Friday, 4 July 2014

But you may get what They think That You Need, Mind maniplulation FaceBook Style or is it ScarFolk Style

Popular new DotCom  is the new leader in exploring psychological frontiers.

This represents the true value of peer review.

A truly valid scientific experiment should be easily repeated to fully validate the original.
No longer just a theory. Now available with modern metrics to help you track the effects of your business advertising dollars.

Eventually this and  other such helpful DotCom's will achieve profitability by extorting selling your own private information back to you for ....well, a lot!

A new bench mark for trust


"We Won't Forget. So You Can't" (1973)

Illicitly and unconstitutionally spying on a whole nation requires an enormous amount of taxpayers' money. That is why, in 1973, Scarfolk started a scheme to sell surveillance data to the public, the actual object of the aforementioned spying.


By 1970, Scarfolk Council had bugged every room, every street, every public and private space. Even forests, beaches and bouncy castles were wiretapped. Every moment of every resident's life was recorded and archived in vast bunkers in the mountains of Snowdonia and abroad.


All this information was subcontracted to a consortium of corporations called RIMPS that used the data to exploit citizens' psychological weaknesses and/or blackmail them into acts of personal depravity for entertainment. These acts were televised and had viewing figures of millions per broadcast. Many people became household names as shame and celebrity became synonymous.

Sunday, 22 June 2014

Sports Concussion: Let's study,again, what we already know. Act later!

This article is from the In-Depth Report Science and Soccer's World Cup

Obama to Host Sports Concussion Summit

The White House supports new funding for youth-focused head injury research



Bureau of Labor Statistics
Pres. Barack Obama has his head in the game—that game being football. And soccer. And actually any sport that fuels an elevated risk of head injury, as will be the focus of a summit set for Thursday on sports concussions. The gathering of some 200 sports officials, clinicians, parents, coaches, school officials and youth athletes will feature discussions on how to address head injuries in youth sports as well as new biomedical findings on youth concussions. The meeting comes after the Institute of Medicine (IOM) and the National Research Council last fall released a report on sports-related concussions, laying out significant gaps in concussion research and highlighting a concerning paucity of information on concussions in youth athletes.

The conference, “Healthy Kids and Safe Sports Concussion Summit,” is set against a backdrop of mounting concerns about the health impacts of sports-related head injuries, especially among children. A new report published in JAMA: The Journal of the American Medical Association earlier this month found that head injuries led an estimated 2.5 million people to visit a U.S. emergency room in 2010, and about one third of the cases were children.

The event for Thursday grew from conversations between the president and White House Press Secretary Jay Carney, according to administration officials. Carney and Obama are parents of relatively young children, and they also tend to talk about their shared love of professional sports. Carney’s son wants to play football and his daughter plays soccer, he told reporters on a press call.

The goal of the summit is to raise awareness about when youth players need to be taken out of a game to prevent further brain injury. Many of the new research efforts that will be rolled out by private partners and the federal government aim to fill the gaps identified by the IOM report.

Along these lines, the Department of Defense and National Collegiate Athletic Association (NCAA) plan to launch a $30-million effort to fund studies on concussion and head-impact exposure among college-age athletes with a multisite longitudinal clinical study on concussion risks, treatment and management. By the third year of the study some 37,000 college-age athletes should be included, according to administration officials. The NCAA and Defense also plan to produce new education materials and identify targets for affecting change in the culture and behavior of college student–athletes and young adults at risk of concussions.

The National Football League is also committing another $25 million over the next three years to support projects aimed at promoting youth sports safety and pilot programs to expand access to athletic trainers in schools. (The league already committed $30 million to head-injury research.) In addition, the National Institutes of Health will also announce a new longitudinal research study to measure the chronic effects of repetitive concussions. That effort will be supported by $16 million of the previously announced NFL funds.

The IOM report had also pointed out that there continues to be no good data set on youth concussion rates or way to conduct good regular surveillance in this area. To that end, the White House will announce that the University of California, Los Angeles, will launch a $10-million effort that will support initial research informing the development of a future national surveillance system that would contain accurate figures about the incidence of youth sports–related concussions.

Professional athletes, too, have rallied around addressing concussion issues in recent years. Last year the NFL and thousands of players who sued the league for concussion damage reached a settlement for $765 million. The memory lapses players think are linked to the hits they took on the field can start relatively young. Brett Favre, the former NFL quarterback, said in an October 2013 interview with a Washington, D.C., radio station that at the age of 44 he could not recall an entire season of his daughter’s youth soccer games.

Players have also noted a culture that prompts them to keep playing or come back too soon after a concussion. Despite “return to play” laws now in place in all 50 states, which typically mandate youth and high school athletes must leave the field if they are suspected of having a concussion and return only after a medical examination by a health professional, the incentive to keep playing—especially if students are trying to impress recruiters—remains strong, and players may not admit their concussion symptoms.

At the summit Pres. Obama will be introduced by a female soccer player who has suffered a number of concussions, according to the White House. “Our focus here is on giving parents information that they need to help make judgments about how their kids can be safe,” said Jennifer Palmieri, White House communications director. “Our focus is not on professional sports.”
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lesizz May 30, 2014, 8:25 PM
" laying out significant gaps in concussion research "
Well, ok, but how about the inaction on research already done? No use doing the research if the federal government is not responsive:
Senseless:
http://www.bicycling.com/senseless/index.html?cm_mmc=Twitter-_-Bicycling-_-Content-Story-_-senseless

Screen All patients with post concussion , Sports related and otherwise.Consensus is that universal screening should be recommended in all patients with moderate-to-severe TBI

Endocrine evaluation of patients after brain injury: what else is needed to define specific clinical recommendations?

Gemma Sesmilo, Irene Halperin, Manuel Puig-Domingo
Servei d’Endocrinologia, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
Keywords
 
Consensus is that universal screening should be recommended in all patients with moderate-to-severe TBI

Brain injury, Growth hormone deficiency, Hypogonadism, Hypopituitarism


Read PDF

INTRODUCTION

Brain injury (BI), both head trauma (TBI) and subarachnoid hemorrage (SAH), has consistently been recognized as an important cause of pituitary dysfunction.1 

 Different studies have estimated that 20-50% of patients who have suffered BI will develop some degree of hypopituitarism.1-9 The high incidence of BI ranks it as potentially the most important cause of hypothalamic-pituitary dysfunction. Although many efforts have been made to explore and define the management of BI patients from the endocrine standpoint, some important questions still remain.

In 2005, a group of experts drew up a Consensus Statement, which included a review of the knowledge on BI induced hypopituitarism and proposed different measures to increase awareness of the problem.10 General recommendations regarding management of patients in this setting were put forward. Recently, Agha and Thompson3 carefully reviewed the new evidence in the field and offered clinical recommendations, although no specific protocol was defined3. These two review articles did not specifically address SAH.

The aim of the present commentary is to underscore which aspects of BI related pituitary dysfunction need further research before specific clinical recommendations are formulated and to highlight practical points in the clinical management of these patients after the acute admission phase.

WHO SHOULD BE SCREENED?

According to the available data, there is consensus that universal screening should be recommended in all patients with moderate-to-severe TBI (Glasgow Coma Scale- GCS- 3 to 12),3,10 although patients with severe disability (vegetative states) who will not benefit from hormonal replacement therapy are excluded from non-vital hormone deficiency assessment. In mild cases (GCS ≥13), screening is indicated only if there are signs or symptoms of pituitary dysfunction. Similarly, universal screening in all patients with SAH who may potentially benefit from hormones replacement therapy is also recommended.

Universal screening as opposed to selective screening based on clinical characteristics. Here we face the first unresolved question: are there specific symptoms and signs in patients with BI related hypopituitarism? 
 Most prospective studies have not provided systematic clinical data on patients with BI with and without hormone deficiencies.4,11-13 Agha reported hormonal outcome in 102 consecutive TBI survivors 6 to 36 months after the event, clinical evaluation of patients being carried out via a questionnaire related to the Quality of Life as a measure of growth hormone deficiency (AGHDAQol).11 There were no differences in quality of life between GH deficient and GH sufficient patients. Leal-Cerro selected patients with a custom-made questionnaire; although no data regarding the questionnaire were provided 33% of the patients showed no signs or symptoms of hypopituitarism according to the questionnaire. Of the remainder, 24.7% showed some form of hypopituitarism upon testing8. To date, the majority of studies have failed to identify clinical predictors of pituitary dysfunction.3,4,7-9,12 However, Bondanelli et al found a relationship between pituitary dysfunction and the severity of the BI evaluated by the GCS,5 while Benvenga, in a retrospective review, found an association of the occurrence and the duration of coma with the severity of the BI.1

Clinical evaluation of hypopituitarism is difficult because signs and symptoms may be subtle and unspecific and may mimic the neuropsychological sequellae of TBI.10,14 Besides, clinical characteristics of mild hypogonadism, hypothyroidism or hypoadrenalism, or mild general hypopituitarism may be difficult to recognize. This is the reason why universal screening with baseline hormonal assessment seems to be the most reasonable approach.3,10 Furthermore, efforts should be made in future clinical studies to define clinical characteristics of hypopituitarism in patients with TBI and to identify clinical variables that may predict pituitary dysfunction. Since hypogonadism, hypoadrenalism and hypothyroidism are easier to diagnose than growth hormone deficiency (GHD) with basal testing, it is important to define a clinical protocol to determine which patients will benefit from GHD screening. In the absence of a simple validated questionnaire of hypopituitarism, the AGDAQoL test may be a useful tool, albeit non-specific, to identify low quality of life that may be due to GHD, which is the most prevalent pituitary deficiency 12 months after TBI.4,15

In summary, universal hormonal screening should be conducted in all patients with moderate-to-severe TBI, in all patients with SAH and in any degree of TBI when there is clinical suspicion. Patients in the vegetative state who are unlikely to benefit from hormone therapy are excluded from non-vital hormone assessment. It is advisable that a short clinical scale for hypopituitarism evaluation be defined. The AGHDAQoL may be useful in quality of life evaluation.

HOW SHOULD PATIENTS BE EVALUATED?


Baseline hormonal testing should be performed in all patients. Screening for hypopituitarism will include tests listed in Table 1 with the following considerations:

A. Pituitary-gonadal axis

The pituitary-gonadal axis in men is evaluated with LH, FSH and testosterone. In women with a history of regular menstrual periods, no assessment is needed; however, in women with menstrual problems or amenorrea, LH, FSH and estradiol have to be measured.

B. Pituitary-adrenal axis

Pituitary-adrenal evaluation is performed with early morning plasma cortisol measurement. Cut-off values for the diagnosis of adrenal insufficiency are different in the acute admission phase from those in outpatient evaluation. Acute cortisol levels <200 nmol/L (7.24 µg/dl) suggest ACTH deficiency and replacement therapy is indicated; between 200 and 400 nmol/L (14.5 µg/dl), clinical judgement should be applied to decide which patients need treatment16. After 3-6 months, baseline cortisol under 98 nmol/L (3.5 µg/dl) is diagnostic of hypoadrenalism, over 285 nmol/L (10 µg/dl) rules out adrenal deficiency and between 3.5 and 10 µg/dl requires provocative testing.15,17 ACTH stimulation tests (low and standard dose) have been found to be of poor reliability in the diagnosis of adrenal deficiency in patients with baseline cortisol between 3.5 and 10 µg/dl;18 therefore, the Insulin Tolerance test (ITT) will be done when not contraindicated. The CRH test in one study yielded 96% specificity but poor sensitivity (76%), using a cut-off cortisol response of ≤377 nmol/L (13.6 µg/dl),17 and may be considered when the ITT is contraindicated.

C. Pituitary-thyroid axis

TSH, free T4 and free T3 measurements are required in the assessment of central hypothyroidism;19 however, studies have shown that in other causes of central hypothyroidism, including cranial irradiation and pituitary tumors, baseline testing had a poor sensitivity of 73%.19-21 This is an issue that has not been specifically addressed in the context of TBI. Most prospective studies have included only one basal thyroid function measurement. Leal-Cerro did TRH stimulation testing to confirm central hypothyroidism only in those patients who already showed low FT4; therefore, sensitivity of the dynamic test as compared to the basal values cannot be assessed.8 Lieberman et al did TRH testing in 27 of 70 adults after TBI.9 Of the 15 patients with low FT4 and/or TSH, 6 underwent TRH testing and 3 of them had subnormal TSH response. Clinical scales (Billewicz or that modified by Zulewski) are not sensitive either, but can be useful in monitoring signs and symptoms.22 More studies are essential to clarify which is the best way to diagnose hypothyroidism in BI and whether the TRH test should be included in clinical protocols. In the meantime, we propose use of baseline thyroid function tests (TSH, FT4 and FT3) and repetition of the measurement in any case with clinical suspicion of hypothyroidism even in the presence of one set of normal tests.

D. Growth hormone assessment

There is no doubt that gonadal, thyroid and adrenal deficiencies should be ruled out and treated. However, whether GHD—in patients with completed linear growth—in the context of BI should be treated and when treatment should be commenced requires more specific studies. This is a crucial issue, since GHD is not easily diagnosed with basal testing. The largest systematic prospective study of pituitary function after BI4 found that GHD is the most common pituitary deficit; 20 and 22% of patients (TBI and SAH, respectively) had isolated severe GHD at 12 months. To rule out GHD, provocative testing is necessary.23 Universal provocative testing in all patients with moderate-to-severe TBI is both troublesome and expensive for the patient. Moreover, since patients with TBI are young, sometimes without previous morbidity, TBI has a major impact in terms of long-term medical care. We have observed that many patients with TBI are reluctant to undergo dynamic blood testing or any further medical evaluation. Before including dynamic testing in routine protocols, clinical consequences of GHD in these patients should be more precisely defined and the effects of GH treatment in this setting need to be proven in randomised clinical trials. Clinical studies are ongoing and their results are needed before specific recommendations are formulated. For the time being, we propose that the measurement of IGF-1 be used to identify GHD (due to its high specificity) and the AGHDAQoL be used to identify which patients may benefit from GH therapy. Therefore, provocative GH testing, carried out when other hormones have been replaced and at the appropriate time to rule out transitory hormone deficits, may be worthwhile.

The only available data to date regarding GH treatment in TBI patients are derived from analysis of the KIMS epidemiological study.24 In this study, patients with GHD after TBI who received GH replacement therapy were shorter than hypopituitary patients due to other causes, suggesting that GHD management was delayed. Patients in KIMS with TBI-induced pituitary dysfunction usually had 3 additional pituitary deficiencies, which is the least common situation found in recent prospective studies of TBI patients. Data on isolated GHD in TBI patients are consequently lacking and are needed before universal GH provocative testing is recommended. However, special attention should be paid to TBI in pediatric or adolescent patients who have not completed linear growth. Such patients should be studied and GHD should be ruled out.

Which is the best provocative test to diagnose GHD in TBI patients is another important unresolved issue. The insulin tolerance test (ITT) is the gold standard but it is sometimes contraindicated in this setting. Tests using GHRH plus arginine or secretagogues may miss hypothalamic causes of GHD, which may be frequent according to pathology studies.6 Therefore, when GH deficiency is suspected and GH treatment is considered, the ITT, when not contraindicated, is the best choice. When the ITT is contraindicated, the glucagon test or tests that use GHRH can be considered, although the former yields some false positive results (0 to 16% according to different studies)9,25 while with GHRH tests a proportion of false negative results are expected.

WHEN SHOULD THE HORMONAL EVALUATION BE PERFORMED?


Adrenal insufficiency should be evaluated any time it is suspected, including the acute admission phase.2 Adrenal and thyroid function should be systematically studied at 3-6 months after the event, or whenever symptoms are present.3,10 The gonadal axis can take some time to recover after the stress. There are no specific data on the clinical consequences of delaying gonadal replacement treatment, but taking into account the potential benefit in body composition and exercise capacity, it would be advisable to treat confirmed hypogonadism when it is present at 3-6 months after the episode. Therefore, universal gonadal evaluation is advised at 3-6 months, simultaneously with thyroid and adrenal function evaluation. If these hormonal axes are normal or abnormal, should patients be re-tested at 12 months? According to Agha,11 in patients with normal anterior pituitary function at 3-6 months no further assessment is needed. In contrast, Aimaretti et al12 in their prospective study showed that new hormonal deficiencies appeared after 3 months of the BI episode and some deficiencies present at 3-6 months (particularly GH and gonadal deficiencies) proved transitory. Therefore, clinical monitoring of patients with normal results at 3-6 months is advised to detect who may need hormonal testing thereafter. Reassessment of thyroid, adrenal and gonadal function at 12 months should be carried out in patients with abnormal results at 3-6 months to rule out transitory deficiencies. GH deficiency should be evaluated after other pituitary hormone deficiencies are adequately managed. In adult patients, GH evaluation will be performed 12 months after the episode, or whenever symptoms are present and a treatment benefit is expected. In pediatric patients, timing of GHD study will depend on the presence of other pituitary deficiencies and on clinical characteristics. In the case of multiple deficiencies, a GHD study may be done 3-6 months after the episode. If no other pituitary deficiencies are present, growth velocity should be monitored 6-12 months after the BI episode before GH stimulation tests are performed. Until more data are available, a trial of GH treatment is warranted in cases with proven GHD and symptoms attributable to GHD. There are no data to support further endocrine follow-up beyond 12 months in patients with normal pituitary function since prospective studies have a maximum follow-up of 1 year. However, long-term clinical monitoring of these patients is advised. Based on current findings a new algorithm for endocrine assessment is proposed (Figure 1).



Figure 1. Recommended algorithm for endocrine assessment after brain injury (BI). See text for details.

WHO SHOULD EVALUATE PATIENTS FOR POSSIBLE HORMONE DEFICIENCY?

It is critical that front-line specialists who take care of these patients (neurosurgeons, trauma surgeons and rehabilitation physicians) be aware of the problem; however, given the high prevalence of TBI induced hormonal deficiencies and the non-specificity of clinical signs and symptoms, systematic endocrine referral 3 to 6 months after BI is recommended. It is advisable to define multidisciplinary cost-effective protocols in which first-line specialists order baseline pituitary function tests and endocrinologists do the clinical evaluation and interpret the hormonal results.

SUMMARY AND CONCLUSIONS

Although much has been learnt about the endocrine consequences of TBI, many questions still remain before specific practical recommendations may be advanced in terms of evaluation and treatment of such patients. Efforts should be made to define summarized clinical scales to be used for screening and treatment purposes. Universal evaluation with basal hormonal testing is advised in all patients with SAH, in patients with moderate-to-severe TBI and in all cases of TBI with clinical symptoms suggestive of hypopituitarism. Adrenal, gonadal and thyroid function assessment is recommended 3 to 6 months after the episode. Adrenal and thyroid should be studied any time if symptoms are present. Whether thyroid assessment needs provocative testing with TRH needs to be clarified. Reassessment at 12 months should be performed in patients with altered function at 3-6 months and in those with previous normal function but clinical suspicion of hypopituitarism. Provocative testing for GHD may be considered 12 months after the episode, when other pituitary deficiencies are being treated and stable and when a treatment benefit is expected, although scientific evidence of benefit from GH replacement treatment in this setting is lacking. GHD should be ruled out in all patients with open epiphyses. The AGHDAQoL may help to select adult patients for provocative testing. It is advisable that front-line specialists select patients for study, order baseline pituitary function tests and refer patients to specialised endocrine care for data interpretation and eventual follow-up.

REFERENCES

1. Benvenga S, Campenni A, Ruggeri RM, Trimarchi F, 2000 Clinical review 113: Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85: 1353-1361.
2. Agha A, Rogers B, Mylotte D, et al, 2004 Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf) 60: 584-591.
3. Agha A, Thompson CJ, 2006 Anterior pituitary dysfunction following traumatic brain injury (TBI). Clin Endocrinol (Oxf) 64: 481-488.
4. Aimaretti G, Ambrosio MR, Di Somma C, et al, 2005 Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab 90: 6085-6092.
5. Bondanelli M, De Marinis L, Ambrosio MR, et al, 2004 Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 21: 685-696.
6. Kornblum RN, Fisher RS, 1969 Pituitary lesions in craniocerebral injuries. Arch Pathol 88: 242-248.
7. Kreitschmann-Andermahr I, Hoff C, Saller B, et al, 2004 Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 89: 4986-4992.
8. Leal-Cerro A, Flores JM, Rincon M, et al, 2005 Prevalence of hypopituitarism and growth hormone deficiency in adults long-term after severe traumatic brain injury. Clin Endocrinol (Oxf) 62: 525-532.
9. Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ, 2001 Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86: 2752-2756.
10. Ghigo E, Masel B, Aimaretti G, et al, 2005 Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj 19: 711-724.
11. Agha A, Rogers B, Sherlock M, et al, 2004 Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 89: 4929-4936.
12. Aimaretti G, Ambrosio MR, Di Somma C, et al, 2004 Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury. Clin Endocrinol (Oxf) 61: 320-326.
13. Tanriverdi F, Senyurek H, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F, 2006 High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma. J Clin Endocrinol Metab 91: 2105-2111.
14. LaChapelle DL, Finlayson MA, 1998 An evaluation of subjective and objective measures of fatigue in patients with brain injury and healthy controls. Brain Inj 12: 649-659.
15. McKenna SP, Doward LC, Alonso J, et al, 1999 The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res 8: 373-383.
16. Agha A, Sherlock M, Thompson CJ, 2005 Post-traumatic hyponatraemia due to acute hypopituitarism. QJM 98: 463-464.
17. Schmidt IL, Lahner H, Mann K, Petersenn S, 2003 Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab 88: 4193-4198.
18. Maghnie M, Uga E, Temporini F, et al, 2005 Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. Eur J Endocrinol 152: 735-741.
19. Ferretti E, Persani L, Jaffrain-Rea ML, Giambona S, Tamburrano G, Beck-Peccoz P, 1999 Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab 84: 924-929.
20. Rose SR, Lustig RH, Pitukcheewanont P, et al, 1999 Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. J Clin Endocrinol Metab 84: 4472-4479.
21. Alexopoulou O, Beguin C, De Nayer P, Maiter D, 2004 Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol 150: 1-8.
22. Zulewski H, Muller B, Exer P, Miserez AR, Staub JJ, 1997 Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab 82: 771-776.
23. Biller BM, Samuels MH, Zagar A, et al, 2002 Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87: 2067-2079.
24. Casanueva FF, Leal A, Koltowska-Haggstrom M, Jonsson P, Goth MI, 2005 Traumatic brain injury as a relevant cause of growth hormone deficiency in adults: A KIMS-based study. Arch Phys Med Rehabil 86: 463-468.
25. Gomez JM, Espadero RM, Escobar-Jimenez F, et al, 2002 Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 56: 329-334.

Address for correspondence:
Gemma Sesmilo, Servei d’Endocrinologia, Hospital Clínic, C/Villarroel 170, 08036 Barcelona, Spain, Tel.: 34 93 227 9846,
Fax: 34 93 451 66 38, e-mail: 30064gsl@comp.es

Received 12-09-06, Revised 22-02-07, Accepted 10-03-07

Wednesday, 4 June 2014

Monoculture ;You Can Always Get What You Want. But You May Not Get What You Need.



It means more than a happy coincidence. And it's under threat from the internet.


From INTELLIGENT LIFE magazine, January/February 2012

See; Monoculture, everything boiled down to one same message

Ian Leslie explains


One day in 1945, a man named Percy Spencer was touring one of the laboratories he managed at Raytheon in Waltham, Massachusetts, a supplier of radar technology to the Allied forces. He was standing by a magnetron, a vacuum tube which generates microwaves, to boost the sensitivity of radar, when he felt a strange sensation. Checking his pocket, he found his candy bar had melted. Surprised and intrigued, he sent for a bag of popcorn, and held it up to the magnetron. The popcorn popped. Within a year, Raytheon made a patent application for a microwave oven.


The history of scientific discovery is peppered with breakthroughs that came about by accident. The most momentous was Alexander Fleming’s discovery of penicillin in 1928, prompted when he noticed how a mould that floated into his Petri dish killed off the surrounding bacteria. Spencer and Fleming didn’t just get lucky. Spencer had the nous and the knowledge to turn his observation into innovation; only an expert on bacteria would have been ready to see the significance of Fleming’s stray spore. As Louis Pasteur wrote, “In the field of observation, chance favours only the prepared mind.”

The word that best describes this subtle blend of chance and agency is “serendipity”. It was coined by Horace Walpole, man of letters and aristocratic dilettante. Writing to a friend in 1754, Walpole explained an unexpected discovery he had just made by reference to a Persian fairy tale, “The Three Princes of Serendip”. The princes, he told his correspondent, were “always making discoveries, by accidents and sagacity, of things which they were not in quest of…now do you understand Serendipity?” These days, we tend to associate serendipity with luck, and we neglect the sagacity. But some conditions are more conducive to accidental discovery than others.

What's a flâneur to do?


Today’s world wide web has developed to organise, and make sense of, the exponential increase in information made available to everyone by the digital revolution, and it is amazingly good at doing so. If you are searching for something, you can find it online, and quickly. But a side-effect of this awesome efficiency may be a shrinking, rather than an expansion, of our horizons, because we are less likely to come across things we are not in quest of.

When the internet was new, its early enthusiasts hoped it would emulate the greatest serendipity machine ever invented: the city. The modern metropolis, as it arose in the 19th century, was also an attempt to organise an exponential increase, this one in population. Artists and writers saw it as a giant playground of discovery, teeming with surprise encounters. The flâneur was born: one who wanders the streets with purpose, but without a map. 

Most city-dwellers aren’t flâneurs, however. In 1952 a French sociologist called Paul-Henry Chombart de Lauwe asked a student to keep a journal of her daily movements. When he mapped her paths onto a map of Paris he saw the emergence of a triangle, with vertices at her apartment, her university and the home of her piano teacher. Her movements, he said, illustrated “the narrowness of the real Paris in which each individual lives”.

To some degree, the hopes of the internet’s pioneers have been fulfilled. You type “squid” into a search engine, you land on the Wikipedia page about squid, and in no time you are reading about Jules Verne and Pliny. But most of us use the web in the manner of that Parisian student. We have our paths, our bookmarks and our feeds, and we stick closely to them. We no longer “surf” the information superhighway, as it has become too vast to cruise without a map. And as it has evolved, it has become better and better at ensuring we need never stray from our virtual triangles.

The filter bubble


Google can answer almost anything you ask it, but it can’t tell you what you ought to be asking. Ethan Zuckerman, director of the Centre for Civic Media at Massachusetts Institute of Technology and a long-time evangelist for the internet, points out that it doesn’t match the ability of the printed media to bring you information you didn’t know you wanted to know. He calls the front page of a newspaper a “discovery engine”: the lead story tells you something you’re almost certain to be interested in—the imminent collapse of the global economy, or Lady Gaga’s latest choice of outfit—and elsewhere on the page you learn that revolution has broken out in a country of whose existence you were barely aware. Editors with an eye for such things, what Zuckerman calls “curators”, are being superseded by “friends”—people like you, who probably already share your interests and world view—delivered by Facebook. Twitter is better at leading us to the interests of people beyond our social circle, but our tendency to associate with others who think in similar ways—what sociologists call our “value homophily”—means most of us end up with a feed that feels like an extended dinner party.

One reason why television viewing has held up relatively well, defying predictions of its demise, is that, compared with the internet, it is good at serendipity. Danny Cohen is in charge of BBC1, Britain’s most-viewed channel. He told me that a new programme on a difficult or obscure subject can still inherit a substantial audience from a popular show. This is, in some ways, a mysterious phenomenon. “I could understand it when changing the channel meant getting off the sofa,” says Cohen. “But now?” Despite remote controls and far more channels, we still willingly succumb to the choices of the broadcasting curators.
Cohen worries that even as the volume of media has grown exponentially, “our propensity to explore it is diminishing”. Driven by the needs of advertisers keen to hit ever more tightly delineated targets, today’s internet plies us with “relevant” information and screens out the rest. Two different people will receive subtly different results from Google, adjusted for what Google knows about their interests. Newspaper websites are starting to make stories more prominent to you if your friends have liked them on Facebook. We spend our online lives inside what the writer Eli Pariser calls “the filter bubble”.

To escape it, we can leave our screens and walk outside. But some of our most serendipitous spaces are under threat from the internet. Wander into a bookshop in search of something to read: the book jackets shimmer on the table, the spines flirt with you from the shelves. You can pick them up and allow their pages to caress your hands. You may not find the book you wanted, but you will walk out with three you didn’t. Amazon will have your book too, but its recommendation engine doesn’t even come close to delivering the same stimuli. Similarly, a librarian isn’t as efficient as a search engine, his memory isn’t nearly as capacious, but he may still be better at making suggestions to a reader in search of—well, something.
But there is a reason why Amazon is successful and bookshops are closing: in a world of infinite choice, efficiency is hard to resist. The pleasures of the bookshop or the library are easily outgunned by the knowledge that we can order or download a book instantly, or find the information we’re looking for within seconds. Serendipity, on the other hand, is, as Zuckerman says,  “necessarily inefficient”. It is a fragile quality, vulnerable to our desire for convenience and speed. It also requires a kind of planned vagueness. Digital systems don’t do vagueness very well, and our patience with it seems to be fading.
Google’s aim is to organise the world’s information and democratise access to it. But when everyone can get the same information in more or less the same way, it becomes harder to be original; innovation thrives on the serendipitous collision of ideas. Zuckerman told me about a speech on serendipity he recently gave to an audience of investment managers. As he started on his theme he feared he might lose their attention, but he was pleasantly surprised to find that they hung on every word. It soon became clear why. “In finance, everyone reads Bloomberg, so everyone sees the same information.” Zuckerman said. “What they’re looking for are strategies for finding inspiration from outside the information orbit.”

The internet has become so good at meeting our desires that we spend less time discovering new ones. To update the Rolling Stones, you can always get what you want. But you may not get what you need. 

Ian Leslie works in advertising, is the author of "Born Liars" and tweets as @mrianleslie
Illustration by Brett Ryder



Monday, 2 June 2014

You can always get what you want. But you may not get what you need.



In Search of Serendipity

 

It means more than a happy coincidence. 

And it's under threat from intuitive web searches 

From INTELLIGENT LIFE magazine, January/February 2012

One day in 1945, a man named Percy Spencer was touring one of the laboratories he managed at Raytheon in Waltham, Massachusetts, a supplier of radar technology to the Allied forces. He was standing by a magnetron, a vacuum tube which generates microwaves, to boost the sensitivity of radar, when he felt a strange sensation. Checking his pocket, he found his candy bar had melted. Surprised and intrigued, he sent for a bag of popcorn, and held it up to the magnetron. The popcorn popped. Within a year, Raytheon made a patent application for a microwave oven.

The history of scientific discovery is peppered with breakthroughs that came about by accident. The most momentous was Alexander Fleming’s discovery of penicillin in 1928, prompted when he noticed how a mould that floated into his Petri dish killed off the surrounding bacteria. Spencer and Fleming didn’t just get lucky. Spencer had the nous and the knowledge to turn his observation into innovation; only an expert on bacteria would have been ready to see the significance of Fleming’s stray spore. As Louis Pasteur wrote, “In the field of observation, chance favours only the prepared mind.”

The word that best describes this subtle blend of chance and agency is “serendipity”. It was coined by Horace Walpole, man of letters and aristocratic dilettante. Writing to a friend in 1754, Walpole explained an unexpected discovery he had just made by reference to a Persian fairy tale, “The Three Princes of Serendip”. The princes, he told his correspondent, were “always making discoveries, by accidents and sagacity, of things which they were not in quest of…now do you understand Serendipity?” These days, we tend to associate serendipity with luck, and we neglect the sagacity. But some conditions are more conducive to accidental discovery than others.

Today’s world wide web has developed to organise, and make sense of, the exponential increase in information made available to everyone by the digital revolution, and it is amazingly good at doing so. If you are searching for something, you can find it online, and quickly. But a side-effect of this awesome efficiency may be a shrinking, rather than an expansion, of our horizons, because we are less likely to come across things we are not in quest of.

When the internet was new, its early enthusiasts hoped it would emulate the greatest serendipity machine ever invented: the city. The modern metropolis, as it arose in the 19th century, was also an attempt to organise an exponential increase, this one in population. Artists and writers saw it as a giant playground of discovery, teeming with surprise encounters. The flâneur was born: one who wanders the streets with purpose, but without a map.

Most city-dwellers aren’t flâneurs, however. In 1952 a French sociologist called Paul-Henry Chombart de Lauwe asked a student to keep a journal of her daily movements. When he mapped her paths onto a map of Paris he saw the emergence of a triangle, with vertices at her apartment, her university and the home of her piano teacher. Her movements, he said, illustrated “the narrowness of the real Paris in which each individual lives”.

To some degree, the hopes of the internet’s pioneers have been fulfilled. You type “squid” into a search engine, you land on the Wikipedia page about squid, and in no time you are reading about Jules Verne and Pliny. But most of us use the web in the manner of that Parisian student. We have our paths, our bookmarks and our feeds, and we stick closely to them. We no longer “surf” the information superhighway, as it has become too vast to cruise without a map. And as it has evolved, it has become better and better at ensuring we need never stray from our virtual triangles.

Google can answer almost anything you ask it, but it can’t tell you what you ought to be asking. Ethan Zuckerman, director of the Centre for Civic Media at Massachusetts Institute of Technology and a long-time evangelist for the internet, points out that it doesn’t match the ability of the printed media to bring you information you didn’t know you wanted to know. He calls the front page of a newspaper a “discovery engine”: the lead story tells you something you’re almost certain to be interested in—the imminent collapse of the global economy, or Lady Gaga’s latest choice of outfit—and elsewhere on the page you learn that revolution has broken out in a country of whose existence you were barely aware. Editors with an eye for such things, what Zuckerman calls “curators”, are being superseded by “friends”—people like you, who probably already share your interests and world view—delivered by Facebook. Twitter is better at leading us to the interests of people beyond our social circle, but our tendency to associate with others who think in similar ways—what sociologists call our “value homophily”—means most of us end up with a feed that feels like an extended dinner party.

One reason why television viewing has held up relatively well, defying predictions of its demise, is that, compared with the internet, it is good at serendipity. Danny Cohen is in charge of BBC1, Britain’s most-viewed channel. He told me that a new programme on a difficult or obscure subject can still inherit a substantial audience from a popular show. This is, in some ways, a mysterious phenomenon. “I could understand it when changing the channel meant getting off the sofa,” says Cohen. “But now?” Despite remote controls and far more channels, we still willingly succumb to the choices of the broadcasting curators.

Cohen worries that even as the volume of media has grown exponentially, “our propensity to explore it is diminishing”. Driven by the needs of advertisers keen to hit ever more tightly delineated targets, today’s internet plies us with “relevant” information and screens out the rest. Two different people will receive subtly different results from Google, adjusted for what Google knows about their interests. Newspaper websites are starting to make stories more prominent to you if your friends have liked them on Facebook. We spend our online lives inside what the writer Eli Pariser calls “the filter bubble”.
To escape it, we can leave our screens and walk outside. But some of our most serendipitous spaces are under threat from the internet. Wander into a bookshop in search of something to read: the book jackets shimmer on the table, the spines flirt with you from the shelves. You can pick them up and allow their pages to caress your hands. You may not find the book you wanted, but you will walk out with three you didn’t. Amazon will have your book too, but its recommendation engine doesn’t even come close to delivering the same stimuli. Similarly, a librarian isn’t as efficient as a search engine, his memory isn’t nearly as capacious, but he may still be better at making suggestions to a reader in search of—well, something.

But there is a reason why Amazon is successful and bookshops are closing: in a world of infinite choice, efficiency is hard to resist. The pleasures of the bookshop or the library are easily outgunned by the knowledge that we can order or download a book instantly, or find the information we’re looking for within seconds. Serendipity, on the other hand, is, as Zuckerman says,  “necessarily inefficient”. It is a fragile quality, vulnerable to our desire for convenience and speed. It also requires a kind of planned vagueness. Digital systems don’t do vagueness very well, and our patience with it seems to be fading.

Google’s aim is to organise the world’s information and democratise access to it. But when everyone can get the same information in more or less the same way, it becomes harder to be original; innovation thrives on the serendipitous collision of ideas. Zuckerman told me about a speech on serendipity he recently gave to an audience of investment managers. As he started on his theme he feared he might lose their attention, but he was pleasantly surprised to find that they hung on every word. It soon became clear why. “In finance, everyone reads Bloomberg, so everyone sees the same information.” Zuckerman said. “What they’re looking for are strategies for finding inspiration from outside the information orbit.”

The internet has become so good at meeting our desires that we spend less time discovering new ones. To update the Rolling Stones, you can always get what you want. But you may not get what you need.
Ian Leslie works in advertising, is the author of "Born Liars" and tweets as @mrianleslie
Illustration by Brett Ryder

Learn to be a flaneur.
A searching constant tourist in life.
There never was a box.
 



Monday, 26 May 2014

Everything you know about teenage brains is bullshit

Everything you know about teenage brains is bullshit

Kathryn Mills reports that discussion has become dominated by unconvincing 'experts' and scaremongering. The evidence is not in.

Forget what you've heard. We don't know much about how Internet use affects the brain
.
After years of being told that the Internet was rotting my brain, I decided to assess the damage by gathering the scientific evidence.

 My review of the published scientific literature found no evidence that typical Internet use harms the adolescent brain.
I'm a neuroscience student researching human brain development, specifically during the teen years.

 Our brain undergoes a lot of changes between childhood and adulthood, and the lab I work in is interested in how these changes relate to our ability to navigate the social world. It's fun work, especially because many people seem to be as interested in learning about the teen brain as I am.

Whenever I present my research to groups of parents or teachers, I'm usually asked a version of the question: "How are digital technologies affecting teenagers' brains?" Until I conducted this review, I would normally respond with a cautious, slightly dismissive, and utterly unhelpful answer: "We don't know."

Ways of knowing

Teachers possess valuable knowledge about young people and generational trends. Over 2,000 American middle and high school teachers responded to a recent survey by the Pew Research Center asking them how they felt the Internet (and other digital technologies) were affecting their students.

The majority of teachers (87%) felt that Internet use was creating an “easily distracted generation with short attention spans,” and 88% felt that “today’s students have fundamentally different cognitive skills because of the digital technologies they have grown up with.”

While surveys can tell us about how people perceive the world, the scientific method allows us to test these observations for their validity. As E. O. Wilson said, "the heart of the scientific method is the reduction of perceived phenomena to fundamental, testable principles." With this in mind, I set out to review the scientific evidence for the Internet's impact on the brain--specifically the teenage brain.

However, to do so I had to first figure out how to define Internet use.

The Internet

What does it mean to use the Internet?

 The Pew Research Center estimates around 87% of adults and 95% of teens in America are users. But Internet use is made up of multiple activities, and is different from video game use, computer use and screen time (all of which can occur offline). One of the most important parts of the scientific process is defining your variable of interest. For the purposes of this review, I defined Internet use as activities such as information gathering, entertainment, and communication accessed through the medium of the World Wide Web.

What I found

To find out if any scientific research had been conducted on this topic, I performed a simple search in the largest biomedical database for studies including the terms internet, adolescence (or teenager), and brain.
Then I looked through the 134 results to see if they were actually relevant.

 Most were not.

 The two studies I classified as empirical research studies did not measure brain changes in response to Internet use, but included experimental paradigms that could tell us something about the effects of Internet use. The studies that did relate Internet use to brain measures sampled an unrepresentative portion of the population, which means the results of these studies are unlikely to apply to most individuals.

The keyboard and the damage done

The Internet is sometimes compared to drugs like heroin, but I think it is much more like coffee (which an estimated 83% of American adults drink).

The studies that have investigated the effects of Internet use on the adolescent brain have focused on adolescents experiencing serious problems from their Internet use (sometimes referred to as Pathological Internet Use).

It might surprise some to hear that the majority of adolescents (95.6%) do not fall into this category.

Most adolescents, like adults, do not experience serious problems from Internet use. We might be using the Internet every day, but most of us are functional users. What this means is that the studies that have shown brain changes in individuals with disordered Internet use do not apply to most adolescents.

What we do know

While we may not know much about how the Internet affects brain development, there has been extensive work into how different Internet activities relate to the health and well-being of adolescents. Importantly, it is becoming clear that typical Internet use does not displace time spent doing IRL activities, such as participating in sports and clubs.

A review conducted five years ago found that communicating with friends through the Internet is related to increased levels of social connectedness in adolescents. And, as I'm sure many readers are already aware, danah boyd has recently written a fantastic book on social media use in adolescence that goes into unprecedented depth on this topic.

In the review, I describe a few studies that could tell us something about how the Internet might shape our way of interacting with the world. Although these studies cannot tell us if Internet use is creating a generation with “fundamentally different cognitive skills,” they suggest that our way of dealing with information might be changing in a world that favors certain skills.

Shaping the developing brain

Repeated experiences in the world will affect neural architecture on some level; such is the nature of our brain. This is true for a human brain of any age. However, the developing brain contains more capacity for change.
 Since experience partially determines what neural connections are kept and strengthened during adolescence, some adults are concerned that Internet use could be “rewiring” the brains of the current generation.
 This is exactly the kind of evidence that is lacking.

While Internet use is almost always thought of as harming the brain, this narrative is not extended to other activities such as musical training.

When I conducted a similar search, replacing the term Internet with music, I found quite a few studies examining how musical training relates to changes in brain measures and cognitive abilities in representative populations (non-professionals).

Perhaps future research examining Internet use can apply similar methods. However, it's important to note that studies showing simple correlations between brain measures and behavior cannot tell us if the behavior caused the change, or if the brain changes relate to well-being. Only longitudinal studies and studies that include measures of functional outcomes (e.g., cognitive measures and measures of well-being) can do that.

Absence of evidence is not evidence of absence 

 

 Just to be clear: I am not saying Internet use does not affect the developing brain. I just haven't found evidence to suggest that Internet use has or hasn't had a profound effect on brain development.

Also, I'm one scientist. It wouldn't surprise me if I missed relevant studies.

This is why I am maintaining a list of scientific studies relevant to this topic. If you know of any studies that could be added to this list, please submit them here.

 That way, whoever writes the next review can incorporate as much evidence as possible.
 

Conflict of Interest


I grew up on the Internet

Shortly after I gave a presentation on this topic at the 2014 SXSW Interactive Festival, my mother unearthed this video:


As you might be able to tell from her hair and voice, my mother spent a lot of time in the late 80s tech-nerd party scene. She's been working with computers for longer than I have been alive. I know I am biased; I think the Internet can't be so bad because I grew up on the Internet.

Whenever an adult asks me if Internet use is harming the teen brain, I am tempted to reveal that I have been using the Internet since I was 9 years old. I think I'm functional. However, treating anecdote with anecdote isn't going to solve this debate. Also, it's clear that Internet use was a fundamentally different experience back when I was a child (see video).

Fear of Internet will fade 


 As more digital natives populate science and positions of power, the fear that the Internet is harming the teen brain will fade. A newer technology will replace it. We can combat this endless cycle of technofear by including younger voices in debates on topics that concern them.
A great example of scientists listening to young people is a study conducted by Suparna Choudhury and colleagues, in which neuroscientists asked adolescents their thoughts on the science of the adolescent brain.

Open up the discussion

It's my hope that this article, and the review, will provoke discussion. Unfortunately, I feel that the discussion about how the Internet could be affecting brain development has been dominated by adult 'experts'. Young people's experiences and thoughts about this topic are valuable sources of knowledge. Without a doubt, Internet use affects our lives. However, we currently do not know how it is impacting brain development. So if anyone has ideas for experiments to test this, let's hear them.
Illustration: Rob Beschizza / Shutterstock

Published 7:49 am Thu, May 22, 2014

More at Boing Boing

Saturday, 24 May 2014

Does Eye Color Predict Response to Pain?



This coverage is not sanctioned by, nor a part of, the American Pain Society.

Does Eye Color Predict Response to Pain?

Fran Lowry

May 14, 2014


TAMPA, Florida —
 The color of a person's eyes may predict how that person responds to pain.

"There may be certain phenotypes that predict or indicate a person's response to pain stimuli or drug treatment for pain," Inna Belfer, MD, PhD, from the University of Pittsburgh School of Medicine in Pennsylvania, told Medscape Medical News.

"Human pain is correlated with multiple factors like gender, age, and hair color," Dr. Belfer said here at the American Pain Society (APS) 33rd Annual Scientific Meeting.
"Researchers have found that red hair is associated with resistance to anesthetics and also to increased anxiety and darker eye color has been reportedly found to correlate with increased physiologic reactivity and drug-induced pupil dilation."

Dr. Belfer added that her anesthesiology colleagues reported noticing a similar association.
"They said that looking in the eyes of their patients tells them if they can expect more or less trouble during the procedures and they can tell who will develop more severe pain or who will respond differently to anesthesia and analgesia," she said.

To explore this association further, Dr. Belfer and her group studied eye color and pain-related traits in healthy women who were undergoing labor and delivery.

They assessed antepartum and postpartum pain, mood, sleep, and coping behavior in 58 women who gave birth at UPMC Magee Women's Hospital.
The women were grouped into 2 cohorts based on their eye color: 24 women in the dark group (brown or hazel eye color) and 34 women in the light group (blue or green eye color).

The women were profiled by using standard validated surveys, including the Brief Pain Inventory, PROMIS anxiety/depression/sleep scales, the Pain Catastrophizing Scale, and Quantitative Sensory Testing, to measure their response to pain.

The results showed that women with dark-colored eyes showed increased anxiety compared with women with light-colored eyes (P = .01).

Women with dark-colored eyes also trended toward increased sleep disturbance (P = .19) and less improvement in catastrophizing/rumination (P = .15) compared with women with light eye color.

Those with darker eyes also showed trends toward experiencing more pain than women with light eye color, both at rest (P = .28) and during movement (P = .22) after receiving epidural analgesia.

Darker-eyed women were less tolerant of heat pain and were also more likely to be depressed as a result of their pain than were light-eyed women, Dr. Belfer said.

"Due to the small sample size, we can't get compelling evidence for our findings, but we do feel that our study has revealed patterns that warrant further studies. We are going to see if there is a link between eye color and clinical pain in part 2 of this project, in men and in women, and in different pain models other than the labor pain model," Dr. Belfer said.

The reason for any differences in pain response could be genetic, Dr. Belfer said. "I specialize in the molecular physiology of pain and we think that there is a genetic background for these effects," she said.

Genetic Link Interesting

"Essentially what they are looking for are genetic correlates, how genes affect the response to pain," said Gregory W. Terman, PhD, MD, professor of anesthesiology, University of Washington, Seattle, asked by Medscape Medical News to comment on the study.

"This is interesting. If you can identify different genes that may be important, perhaps we can increase our understanding of the pain picture and why there are differences in the amount of pain some people can tolerate.
 In this case, they may be looking for yet another gene that is correlated with increased or decreased pain, and there are quite a few of those around," Dr. Terman, president-elect of the American Pain Society, said.

He agreed that trying to find correlations between patients and pain responses is a promising area of research.

This study was supported by the University of Pittsburgh Department of Anesthesiology Seed Award and New Competitive Medical Research Fund. Dr. Belfer and Dr. Terman have disclosed no relevant financial relationships.
 
American Pain Society (APS) 33rd Annual Scientific Meeting. Abstract 197. Presented May 1, 2014.