Huntington University

The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.

OBJECTIVE: To determine if there is a gender difference in the incidence and outcomes of sport concussion. DESIGN: Critical literature review of sport concussion by gender. INTERVENTION: PubMed and major sports medicine journals were reviewed using the keywords concussion and gender. Articles included in this paper were English prospective surveillance that included concussion as an injury option conducted over the past 10 years, involved data collected by qualified medical personnel (athletic trainers/therapists or medical doctors) and used injury rates as opposed to raw counts. Only data from sports (soccer, basketball and ice hockey) where actions, equipment and most rules were similar between genders were reviewed. RESULTS: For the PubMed search, using "concussion" and "gender" as keywords, there were 51 articles. Ten studies (four in football (soccer), four in basketball and two in ice hockey, including high school, college and professional athletes) were included in the incidence portion of the paper. Nine of the studies showed higher absolute injury rates for female concussion compared to their male counterparts with four of them reaching statistical significance. Five of the studies (two football (soccer), two basketball and one ice hockey) examined concussion mechanism and in all cases, males had a higher absolute percent of player contact concussions while females had a higher absolute percentage of surface or ball contact concussion episodes. Two brain injury and four sport concussion outcome papers were reviewed. Traumatic brain injury outcome was shown to be worse in females than in males for a majority of measured variables; females also are shown to have different baseline and post-concussion outcomes on neuropsychological testing. CONCLUSIONS: After evaluating multiple years of concussion data in comparable sports, the evidence indicates that female athletes may be at greater risk for concussion than their male counterparts. There also is some evidence that gender differences exist in outcomes of traumatic brain injury and concussions. Because concussion is a clinical diagnosis often depending on self reporting and with no established biological marker or consistent symptoms/definitions, and because there is evidence that females are more honest in reporting general injuries than males, it is unclear whether the concussion incidence data, while generally consistent in showing a higher risk in females as compared to males in similar sports, is a true difference or is influenced by a reporting bias.

PURPOSE: The aim of the current work is to provide evidence-based recommendations to practicing physicians and others on the management of the neck in patients with squamous cell carcinoma of the oral cavity and oropharynx. METHODS: ASCO convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2018. Outcomes of interest included survival, regional disease control, neck recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 124 relevant studies to inform the evidence base for this guideline. Six clinical scenarios were devised; three for oral cavity cancer and three for oropharynx cancer, and recommendations were generated for each one. RECOMMENDATIONS: For oral cavity cancers, clinical scenarios focused on the indications for and the hallmarks of a high-quality neck dissection, indications for postoperative radiotherapy or chemoradiotherapy, and whether radiotherapy alone is sufficient elective treatment of an undissected neck compared with high-quality neck dissection. For oropharynx cancers, clinical scenarios focused on hallmarks of a high-quality neck dissection, factors that would favor operative versus nonoperative primary management, and clarifying criteria for an incomplete response to definitive chemoradiation for which salvage neck dissection would be recommended. Consensus was reached and recommendations were made for all six clinical scenarios. Additional information is available at www.asco.org/head-neck-cancer-guidelines .

The 1994 predictive test guidelines for Huntington's disease (HD) were published by an ad hoc Committee comprising representatives from the World Federation of Neurology (WFN) and the International Huntington Association (IHA) 1, 2 shortly after the gene mutation for HD was identified. These guidelines have led the way in setting standards for predictive testing not only for HD, but also for other late onset neurodegenerative diseases such as familial frontotemporal dementia and spinocerebellar ataxias (SCA's). They were also a valuable foundation for good clinical practice for predictive testing for hereditary cancers and other late onset conditions. Having a clear set of recommendations has helped to clarify the predictive test process for both clinicians and family members. Undoubtedly the guidelines have succeeded in their original aims of setting minimum standards for predictive testing, protecting at risk individuals and providing a reference point to help with ethical and clinical dilemmas as they arose. Whilst it is essential after twenty years to review the guidelines in the context of the substantial evidence that has emerged in the intervening years, many of the recommendations remain valid today. The process of reviewing the guidelines was initiated by the European Huntington Disease Network (EHDN) 'Genetic Testing and Counselling' Working Group, formed during the EHDN congress in Dresden in 2007 by Prof Gerry Evers-Kiebooms. The aim of the working group (WG) was to look at communication in relation to genetic test information. Members of the WG include family members, genetic counsellors, psychologists, clinical geneticists, neurologists, and laboratory scientists from over 12 European countries. During the first WG workshop in Leuven (BE) in 2008, attention focused more on the predictive test guidelines. Whilst there was consensus that the guidelines were an excellent and valued resource, gaps were apparent in relation to new evidence and practices that had emerged since 1994. These included new technology such as preimplantation genetic diagnosis (PGD), increased scientific knowledge about HD (understanding of intermediate (IA) and reduced penetrance (RP) alleles, and prodromal signs), the debate surrounding the testing of minors, new opportunities to participate in research and data on individuals' experiences of testing such as post test discrimination. Subgroups were set up to review the current research evidence in relation to six sections of the original guidelines that corresponded to the identified gaps (2.1 Testing of minors; 2.8 Laboratory standard of accuracy; 4.0 Communication of information; 5.2 Information pertaining to the test 7.0 'Prenatal Diagnosis' renamed 'Reproductive options'; 9.0 Post test counselling). The sub-groups comprised WG members with a particular specialism and/or interest in the topic. Family members participated in each of the sub-groups and international participants outside Europe were invited to contribute their expertise on specific topics. Written proposals, debated in plenary discussions, included the rationale for changes and references used by the sub-group. The sub-group members subsequently corresponded by email and drafted updates and additions to the original guidelines. The proposed changes have undergone a lengthy consultation process both through the EHDN website (June–August 2010), where comments to the proposed changes could be posted, and globally through a review from a committee appointed jointly by IHA and WFN (Nov 2010–June 2011). A Town Hall session at the World Congress Meeting on HD in Melbourne in September 2011 provided a forum for the proposals to be presented to the wider HD community. This proved a valuable source of feedback and also drew on the knowledge and input of an expert panel of professionals and family members from countries including South America, Australia and Canada. Following the meeting in September 2011 Prof Raymund Roos, Chair of the WFNHD Research Group, invited a small editorial committee, drawn from the international community, to assist with the final edits. A proposal made at the 2011 World Congress Meeting on HD was for the guidelines to be reviewed every two years in conjunction with the World Congress meeting. Prospectively this will allow all members of the HD community to put forward points for consideration by a committee appointed on behalf of the Chairs of both the IHA and WFNHDRG. This will also ensure that clinical recommendations continue to evolve and reflect changes in our knowledge and practice. The document that follows is the next version of the 1994 predictive test guidelines for HD. It is important to emphasize that these are not intended as rigid rules but rather recommendations to guide and inform practice, based on current evidence and expertise. Finally it is hoped that these proposals will stimulate new discussion about predictive test counselling approaches and how best to serve the needs of individuals and families. New challenges continue to arise in predictive test counselling; for example, how to ensure equity of access to genetic counselling services and how to ensure a new generation of young people from HD families have their say in the way genetic counselling services are provided. REC 1 All persons who may wish to take the test should be given up to date, relevant information in order to make an informed voluntary decision. COM 1 The highest standards of counselling should be available in each country. It is recommended that informed consent for the test be documented with the signature of the person to be tested and the professional responsible for the counselling as a standard medical practice. REC 2 The decision to take the test is the sole choice of the person concerned. No requests from third parties, be they family or otherwise, should be considered. COM 2 The person must choose freely to be tested and not be coerced by family, friends, (potential) partners, physicians, insurance companies, employers, governments, etc. REC 2.1 It is recommended that the minimum age of testing be 18 years. Minors at risk requesting the test should have access to genetic counselling, support and information including discussion of all their options for dealing with being at risk. COM 2.1 REC 2.2 Each participant should be able to take the test independently of his/her financial situation. COM 2.2 Each national lay organization should use its influence with government departments, public and private health insurers, etc, to reach this goal. REC 2.3 Persons should not be discriminated against in any way as a result of genetic testing for Huntington's disease (see also REC 5.3.5). REC 2.4 Extreme care should be exercised when testing would provide information about another person who has not requested the test. COM 2.4 This will arise when an individual(s) at 25% risk request(s) testing with full knowledge that his/her parent does not want to know his/her status. Every effort should be made by the counsellors and the individuals concerned to come to a satisfactory solution of this conflict. REC 2.5 For participants with evidence of a serious psychiatric condition, it may be advisable that testing is delayed and support services put into place. REC 2.6 Testing for HD should not form part of a routine blood investigation without the specific permission of the subject. COM 2.6 Such a specific permission should in principle also be required for symptomatic persons. REC 2.7 Ownership of the test results remains with the person who requested the test. Legal ownership of the stored DNA remains with the person from whom the blood was taken. COM 2.7 The consent form should address this issue. Local legal opinions may be helpful. REC. 2.8 All laboratories are expected to comply with the Organization for Economic Co-operation and Development (OECD) Guidelines for Quality Assurance in Molecular Testing by providing and practicing genetic testing under a quality assurance framework, meet rigorous standards of accuracy, participating in external quality assessment (EQA) schemes and working towards certification and accreditation. COM 2.8 At-risk individuals, family members and the lay organizations can enquire about the quality standards of the laboratory, including, for example, its certification and accreditation status. The lay organizations can also assist persons who want to be or have been tested with their enquiries and concerns. REC 2.8.1 REC 2.9 The counsellors should be specifically trained in counselling methods and form part of a multidisciplinary team. COM 2.9 Such a multidisciplinary team should consist, for example, of a clinical geneticist, genetic counsellor or social worker, neurologist, psychiatrist or psychologist. REC 3 The participant should be encouraged to select a companion to accompany him/her throughout all the different stages: the pre-test, the taking of the test, the delivery of the results and the post-test stage. COM 3 This should be assessed on an individual basis and the presence of a companion may not be appropriate or required in all cases. REC 3.1 The counselling unit should plan with the participant a follow up protocol which provides support during the pre- and post-test stages, whether or not a person chooses to be accompanied by a companion. COM 3.1 Wherever possible, support should be available close to the person's community, and on a remote basis, by phone or telehealth where necessary. REC 4 Testing and counselling should be provided by genetic counselling units knowledgeable about molecular genetic issues in Huntington's disease. These centres should work in close collaboration with the lay organization(s) of the country. COM 4 Often the test will be conducted at a site different from the counselling centre. If no lay organization exists in the country, the centre should contact the IHA. REC 4.1 The laboratory performing the test should not communicate the final results to the counselling team until very close to the time the results are given to the participant. COM 4.1 The aim is to protect the participant from the possibility of counselling bias at any time (see also COM 5.2.6). REC 4.2 As a rule, members of the counselling team or the technical staff should not communicate any information concerning the test and its results to third parties without the explicit permission of the person tested. COM 4.2 Only in the most exceptional circumstances (e.g. prolonged coma or death) may information about the test result, if so requested, be provided to family members whose risk is affected by the result. REC 4.3 Neither the counselling centre nor the test laboratory should establish direct contact with a relative whose DNA may be needed for the purpose of the test without permission of the participant and of the relative. All precautions should be taken when approaching such a relative. REC 4.4 Care should be taken regarding access to clinical reports of the test results. COM 4.4 Consent of the participant should be sought before sending a letter to any physician involved in their care (e.g. family doctor, neurologist, or hospital physician). The possible benefits and drawbacks of sending the result to such physicians should be discussed. These benefits include: post-test support, future clinical care including identification and support around the onset of symptoms, and their symptomatic treatment. The risks include: potential discrimination in economic, social and medical domains, should their medical files be accessed by third parties. COM 5 'Essential information' means information which is absolutely vital to the whole test procedure. COM 5.1 This information should be both written and oral and be provided by the team responsible for the test service. REC 5.1.1 On Huntington's disease, including the wide range of its clinical manifestations, the social and psychological implications, the genetic aspects, reproductive options, availability of treatment, etc. COM 5.1.1 It must be pointed out that at this time no proven prevention, treatment that slows disease progression, or cure is available. REC 5.1.2 On the implications of non-paternity (and non-maternity). COM 5.1.2 Genetic testing may show, or suggest, that the putative parent is not the biological parent; this aspect should be drawn to the attention of the participant and discussed. With the presently available techniques of in vitro fertilization, etc., even occasional non-maternity may occur. REC 5.1.3 On lay organizations, including their documentation on HD, their addresses for help and social contacts, etc. COM 5.1.3 If no lay organization exists in the country, contacts can be made with the IHA or lay organization of a neighbouring country. REC 5.1.4 Psychosocial support and counselling must be available before the test procedure commences. COM 5.1.4 Lay organizations should be mentioned as an additional source of support and information. REC 5.2.1 How the test is done. REC 5.2.2 Possible need for DNA from an affected family member and the possible problems arising from this. COM 5.2.2 Asking an affected person, who may be unaware of or unwilling to acknowledge his/her symptoms, to contribute a blood sample may be an invasion of privacy. REC 5.2.3 The limitations of the test (error rate, uncertain predictive interpretation of some CAG repeat numbers, etc). REC 5.2.4 The counsellor must explain that, although the genetic mutation has been found, at the present time only limited useful information can be given about age at onset or about the kind of symptoms, their severity, or the rate of progression. COM 5.2.4 REC 5.2.5 Pre-test genetic counselling should mention all possible test outcomes, including intermediate and reduced penetrance results, which may be prone to repeat instability and may expand into higher repeat ranges upon transmission to future generations. However, there is insufficient information regarding the magnitude of the risk of expansion for future generations. COM 5.2.5 REC 5.2.6 The predictive test indicates whether someone has or has not inherited the gene mutation, but it does not make a clinical diagnosis of HD if the gene expansion is present. COM 5.2.6 Particular care should be taken with participants who are believed by the clinician to be showing early symptoms of HD; however, persons with evident but unacknowledged symptoms should not automatically be excluded from the test. Rather, they should be offered additional pre and post test support. REC 5.2.7 Pre-test counselling should also outline information on post-test counselling and options for future research participation and care. REC 5.3.1 For the person him/herself. COM 5.3.1 Most participants will adjust to their predictive test result. Some individuals may, however, experience difficulty coping with any of the possible results in the short or long term (including a result in the normal range). Additional counselling should be offered to those at risk of having difficulties with coping (e.g. individuals with a history of psychiatric illness). REC 5.3.2 For the spouse/partner and children. COM 5.3.2. If the participant is not accompanied by his/her spouse/partner during the counselling sessions, there should be particular discussion about the potential impact of the test result on the spouse/partner. It is possible that the genetic test result and/or family history will impact the participants' current or future family members' eligibility for insurance, employment, legal care of and access to children, and adoption. REC 5.3.3 For the affected parent and his/her spouse. COM 5.3.3 The feelings of the affected parent, who may well become aware of the results, must be taken into account. REC 5.3.4 For the other members of the participant's family. COM 5.3.4 Whatever information is obtained, it may influence the feelings of and the relationship with others, with a potential for discrimination in the family. This may include: disrupted patterns of behaviour and interaction, such as communication changes and feelings of altered sense of membership. REC 5.3.5 REC 5.4.1 Not to take the test for the time being. REC 5.4.2 To deposit DNA for research. REC 5.4.3 To deposit DNA for possible future use by family and self. REC 5.4.4 DNA deposited under 5.4 above would be made available to the donor's family members at their request after the death of the donor if it is essential to obtain an informative result. REC 5.4.5 In the case of DNA deposited under 5.4.2 and/or 5.4.3 above, the unit collecting the DNA must provide a written declaration that samples will not be used for purposes other than specified in the said declaration with the exception of the provisions of 5.4.4. REC 6.1 It is important to verify that the diagnosis of HD in the person's family is correct. REC 6.2 Neurological examinations (if possible) and psychological appraisal are considered important to establish a baseline evaluation of each person. This however is not a requirement for participation in predictive testing. COM 6.2 Refusal to undergo these and other additional examinations will not justify the withholding of the test from participants. REC 7.0.1 Preconception counselling should be available to couples where one partner is at risk of HD or is a carrier of the HD gene expansion. COM 7.0.1 The importance of preconception counselling is stressed, because of the timeframe in making a decision about testing during an ongoing pregnancy. Moreover, such preparation may help to decrease the simultaneous requests for presymptomatic and prenatal diagnosis; a very stressful situation due to the limited time available and the potential for consecutive adverse outcomes. REC 7.0.2 Preconception counselling should include discussion around the range of reproductive options available. These options may include proceeding with a pregnancy without testing, prenatal diagnosis (PND) preimplantation genetic diagnosis (PGD), donor insemination and adoption. REC 7.1.1 Couples should be made aware of all the options available to them in pregnancy, including the possibility of prenatal testing. COM 7.1.1 Careful pre-test counselling by an informed professional is necessary in order to ensure that the (future) pregnant woman and her partner are fully aware of the consequences of prenatal testing. All possible test outcomes (full expansion, reduced penetrance, intermediate and normal alleles) should be made clear to the couple. It is preferable for the counselling to take place in a specialized (prenatal or genetics) centre. REC 7.1.2 Direct prenatal testing for the HD mutation is usually only performed if the parent at risk has already been tested. For a possible exception see 7.1.6. REC 7.1.3 PND for an individual with a reduced penetrance allele of the HD gene is justified. REC 7.1.4 PND for an individual with an intermediate allele of the HD gene is justified. COM 7.1.4 There is insufficient information regarding the magnitude of the risk of CAG repeat expansion of intermediate alleles in the transmission to offspring. The risk of expansion into the full penetrance range is small, but may vary with the CAG size of the intermediate allele and the ethnicity of the REC PND should be available as an for couples where the parent does not want to know his/her genetic status. The and of this however, should be in during COM The of PND is that it the possibility of a prenatal test where the parent does not wish to have a predictive test but where the is clear they not wish to have a at risk of HD. The is that the may up an pregnancy where the parent is not a mutation REC Direct prenatal testing of the where one of the is at risk but not to know his/her carrier should be considered where the requests this in pregnancy. COM The only of this is that, in the case of a normal result in the the parent at risk does not know his/her carrier his/her wish not to However, in the case of the gene mutation in the the carrier of the parent at risk will be The possibility of this adverse should be and the for such an before with this test REC The requesting prenatal testing must be informed that if they to the pregnancy whether the is a carrier of the gene expansion or there is no valid for performing the test. COM This is in with the not to test The regarding his/her future to whether or not to undergo a test is if pregnancy is in the case of an prenatal test result. The of the and their to freely on the taken on the basis of the prenatal test result should be and with there is a small, but not risk of to the procedure. REC It is not recommended to the pregnancy of a on the basis of an intermediate allele result. COM COM Genetic in with is a reproductive for people at risk of on a genetic The different of for HD and the different where may be an will be in the specific recommendations regarding for HD. REC. It is recommended to to an carrier of the HD gene expansion or more and his/her partner if there is access to this technology in the where genetic counselling is being provided. COM In is offered to people at risk of on a serious genetic The risk of expansion of an intermediate allele to a reduced or full allele is not but is with an intermediate allele requesting should be offered genetic REC. should be available for couples at risk for with HD. COM The of is that it to the transmission of the HD mutation, at the time the person's wish not to The counselling should address the impact of the about his/her genetic upon the of the future REC. should be COM and ethical in practice it will be to the participant's wish not to the procedure where reproductive physicians would be both to more and to a the risk of having a with HD will be REC. Couples where one partner is already symptomatic should have access to counselling for Psychosocial counselling on the impact upon a of up with a parent with HD in and of the potential in the specific case is an important aspect of the procedure. COM symptomatic is not a an for attention should be given to the of the symptoms of HD upon the future The and coping of the partner are important in this A does to couples where one partner the of HD in being aware of the for future children. REC. REC exceptional circumstances there should be a minimum of one the of the pre-test information and the decision whether or not to take the test. The counsellor should that the pre-test information has been and should take the to be of this. However, contact will only be at the participant's COM Such an is necessary to the person time to the pre-test information in order to make an informed decision. During this from the test centre must be available. testing may an as it is important to testing as early as possible during the pregnancy. REC The result of the predictive test should be as as possible after of the test, on a upon in the the and the person. REC The in which results will be should be the counselling team and the person. REC The participant has the to at any time that the result not be given to REC The results of the test should be given by the counsellor to the person and his/her companion. In remote the result session may be by with a clinician to the participant No result should be given by or by The counsellor must have time to any with the person. REC All post-test provisions (see must be available from the time the test results are REC The and the form of the post-test counselling should be the team and the participant before the of the test, but the participant has the to the the and will vary from person to person, post-test counselling must be available at all REC The counsellor should have contact with the person the first after delivery of the results, of the test result. REC If there has been no contact one of the delivery of the test result, the counsellor should the follow REC It is essential that post-test counselling is made available of the person's financial situation. REC During post-test contact specific information on options, including (if participation in clinical research can be provided. The of prodromal of mutation and their (if could be discussed. COM REC information in should be during the pre-test REC The lay organization has an important to in the post-test The information and support that it can provide should be offered to the participant of whether or to that to the for additional EHDN members, The Testing Group, and the WG

As recently as 5 years ago, very little information on the emotional well-being of adolescents with learning disabilities (LD) was available. However, a great deal of research has been conducted recently and some of the implications are unnerving. Research on self-concept, attributions, anxiety, depression, and suicide among adolescents with LD is examined for the purpose of detecting consistency of indicators concerning these emotional and developmental variables. The research indicates that the emotional development of many adolescents with LD is not notably positive, and these students appear to be at increased risk for severe depression and suicide. The discussion highlights methodological pitfalls and developmental issues. Practical implications are suggested.

We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.

The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.

OBJECTIVE: To assess the effectiveness of free beta-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18. METHODS: Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the combination of nuchal translucency and biochemistry (n = 5809). RESULTS: The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15. 8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0. 9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%. CONCLUSION: First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients.

Mature human erythrocytes were incubated with (14)C-labeled palmitic acid bound to crystalline human albumin. Energy-dependent incorporation of the labeled palmitic acid into cell membrane phospholipids occurred, and various stages in this incorporation were defined. Initially the palmitic acid was rapidy transferred from the albumin to a "superficial" membrane pool of free fatty acid (F-1), which was removable when the cells were washed with defatted albumin. This process was independent of red cell metabolism. The labeled fatty acid then passed into a second "deeper" membrane pool of free fatty acids (F-2), which was not extractable with albumin. This process was energy-dependent and proceeded at a slower rate than the initial transfer from albumin to F-1. Ultimately the labeled fatty acid was incorporated into phosphatides (PL). This process also was dependent upon cellular metabolism. The kinetics of pulse label studies suggest that the processes observed were sequential and that precursor-product relationships exist between the F-1 and F-2 pools and the F-2 and PL pools. [Formula: see text] From the size and specific activities of these pools, calculations of the extent of phospholipid turnover were made. An approximate figure of 2% /hr or 30 nmoles/ml of packed red blood cells per hr was obtained. The figure was further calculated to represent an energy cost to the red blood cell of approximately 5% of the energy available from glycolysis.

Abstract The internal fabric and localized deformation patterns of triaxial sand specimens were investigated using computed tomography (CT). Three displacement-controlled, conventional, drained axisymmetric (triaxial) experiments were conducted on dry Ottawa sand specimens at very low effective confining stresses (0.05, 0.52, and 1.30 kPa) in a microgravity environment aboard the Space Shuttle during the NASA STS-79 mission. CT scanning was performed on these flight specimens, as well as on an uncompressed specimen and a specimen tested in a terrestrial laboratory at 1.30 kPa effective confining stress. CT demonstrated high accuracy in detecting specimen inhomogeneity and localization patterns. Formation of deformation patters is dependent on the effective confining stress and gravity. Multiple symmetrical radial shear bands were observed in the specimens tested in a microgravity environment. In the axial direction, two major conical surfaces were developed. Nonsymmetrical spatial deformation was observed in the 1-G specimen. Analysis tools were developed to quantify the spatial density change. Void ratio variation within and outside the shear bands is calculated and discussed.

A student’s level of self-efficacy and test anxiety directly impacts their academic success (Abdi, Bageri, Shoghi, Goodarzi, & Hosseinzadeh, 2012; Hassanzadeh, Ebrahimi, & Mahdinejad, 2012). When a student doubts themself and their own ability to test well, the students’ sole focus becomes worrying about poor grades and cannot focus on academics (Bandura, 1993). But, little is understood about how test-anxiety and self-efficacy affect short-term success in the classroom. Specifically, how test anxiety and level of self-efficacy directly preceding an exam will affect the exam score. Pre-and post-questionnaires assessing anxiety and self-efficacy immediately before and after a single college exam was completed by 110 college students and exam grades were obtained from the instructor. Results showed a strong relationship between both test anxiety and exam grades, and self-efficacy and exam grades. Further, multiple linear regression analyses showed that exam grade could be predicted by test anxiety and self-efficacy level, and that self-efficacy moderated the effects of anxiety.

In recent years thermodynamic modelling via the CALPHAD method has been extensively applied to industrial alloys of many types.Although pertaining to equilibrium conditions, use has shown that valuable information can be gained for a variety of practical applications.A paper presented at the last Seven Springs meeting gave some theoretical background to the CALPHAD method and described the development of the methodology to Ni-based superalloys.The main purpose of that paper was to provide validation of results against an extensive experimental literature which, at the time, concentrated on 'r'/?" equilibria and liquid/solid equilibria.The present paper will present an extension of the validation process to take into account 11 formation and provide a review and examples of the practical application of the CALPHAD method to industrial alloys.It will expand on some of the topics briefly raised in the previous paper and demonstrate that the CALPHAD route is readily extendable to conditions that depart from equilibrium.It will also be shown that it can be used to provide fundamental input for calculations of physical and mechanical properties.

Abstract During April 2007, a coordinated series of snow measurements was made across the Northwest Territories and Nunavut, Canada, during a snowmobile traverse from Fairbanks, Alaska, to Baker Lake, Nunavut. The purpose of the measurements was to document the general nature of the snowpack across this region for the evaluation of satellite- and model-derived estimates of snow water equivalent (SWE). Although detailed, local snow measurements have been made as part of ongoing studies at tundra field sites (e.g., Daring Lake and Trail Valley Creek in the Northwest Territories; Toolik Lake and the Kuparak River basin in Alaska), systematic measurements at the regional scale have not been previously collected across this region of northern Canada. The snow cover consisted of depth hoar and wind slab with small and ephemeral fractions of new, recent, and icy snow. The snow was shallow (<40 cm deep), usually with fewer than six layers. Where snow was deposited on lake and river ice, it was shallower, denser, and more metamorphosed than where it was deposited on tundra. Although highly variable locally, no longitudinal gradients in snow distribution, magnitude, or structure were detected. This regional homogeneity allowed us to identify that the observed spatial variability in passive microwave brightness temperatures was related to subgrid fractional lake cover. Correlation analysis between lake fraction and Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) brightness temperature showed frequency dependent, seasonally evolving relationships consistent with lake ice drivers. Simulations of lake ice thickness and snow depth on lake ice produced from the Canadian Lake Ice Model (CLIMo) indicated that at low frequencies (6.9, 10.7 GHz), correlations with lake fraction were consistent through the winter season, whereas at higher frequencies (18.7, 36.5 GHz), the strength and direction of the correlations evolved consistently with the penetration depth as the influence of the subice water was replaced by emissions from the ice and snowpack. A regional rain-on-snow event created a surface ice lens that was detectable using the AMSR-E 36.5-GHz polarization gradient due to a strong response at the horizontal polarization. The appropriate polarization for remote sensing of the tundra snowpack depends on the application: horizontal measurements are suitable for ice lens detection; vertically polarized measurements are appropriate for deriving SWE estimates.

INCONEL alloy 625 (UNS N06625) has been widely used for over 50 years in the marine and petroleum industries for applications requiring high strength, fracture toughness, fabricability and resistance to corrosion. By increasing the titanium content of the alloy in the presence of its content of niobium, an alloy that can be significantly strengthened by heat treatment is created. By the precipitation of various secondary phases in an austenitic matrix, INCONEL alloy 725 (UNS N07725) offers the high strength of alloy 718 along with the corrosion resistance of alloy 625. The metallurgy of alloy 725 is discussed along with information about its properties, fabrication, and applications.

Inconel alloy 718 is a relatively new high-strength, weldable alloy that is suitable for service at temperatures from −423 F up to 1300 F. The excellent properties of this alloy over this temperature range result from extensive research on the influences of various elements and heat treatments. This paper describes the metallurgical investigation relating the nature of the alloy to the development of optimum properties.

Computed tomography (CT) and plain radiography of the pelvis were compared in 26 adult patients in whom acetabular fractures or posterior femoral head dislocations were demonstrated or suspected on initial radiographs. The detection of abnormalities of the sacrum, sacroiliac joint, iliac wing, acetabular roof, joint space, anterior pelvic column, posterior pelvic column, posterior acetabular lip, pubic rami, and quadrilateral surface of the ilium by the two methods was compared. The ability of the two techniques to establish the stable fragment was also examined. Three independent readings of each examination for each pelvic region were tabulated, and sensitivity and specificity values were calculated. There was no significant difference between plain radiography and computed tomography in detection of fractures of the iliac wing, anterior pelvic column, posterior pelvic column, and the pubic rami, with high sensitivity and specificity for both examinations. CT was more sensitive than plain radiography in detecting fractures involving the sacrum, quadrilateral surface, acetabular roof, and posterior acetabular lip. In addition, abnormalities of the hip joint space, principally loose bone fragments, were detected more often by CT. Sensitivity of both examinations for abnormalities of the sacroiliac joint was relatively poor, but examinations were highly specific. Determination of the stable fracture fragment(s) was readily accomplished by CT scanning in all 26 patients; in five patients incorrect determinations were made with conventional radiographs alone.

Advanced Glycation Endproducts (AGEs) are a heterogeneous group of molecules produced from non-enzymatic glycation. Accumulation of AGEs in vivo plays an important role in the pathology of chronic human diseases including type-2 diabetes and Alzheimer's disease. Natural AGEs inhibitors such as the pomegranate (Punica granatum) fruit show great potential for the management of these diseases. Herein, we investigated the in vitro anti-glycation effects of a pomegranate fruit extract (PE), its phenolic constituents [punicalagin (PA), ellagic acid (EA) and gallic acid (GA)], and their in vivo derived colonic metabolites [urolithin A (UA) and urolithin B (UB)]. All of the samples showed anti-glycation activities and PE, PA, and EA were more potent inhibitors than the positive control, aminoguanidine. PE and the purified phenolics also exhibited carbonyl scavenger reactivity. Our study suggests that pomegranate may offer an attractive dietary strategy for the prevention and treatment of AGE-related diseases such as type-2 diabetes and Alzheimer's disease.

OBJECTIVES: Social capital, collective efficacy, and religious involvement have each been linked to population health. This study examined the relations between these measures and male/female mortality rates in Hungary. DESIGN: Cross sectional, ecological study. SETTING: 150 sub-regions of Hungary. PARTICIPANTS AND METHODS: 12643 people were interviewed in 2002 (the "Hungarostudy 2002" survey). Social capital was measured by lack of social trust, reciprocity between citizens, and membership in civil organisations. Collective efficacy was measured by survey items from the Project on Human Development in Chicago Neighborhoods. Religious involvement was measured by church attendance. MAIN OUTCOME MEASURE: Gender specific all cause mortality rates for the middle aged population (45-64 years) in the 150 sub-regions of Hungary, provided by the Central Statistical Office (CSO). RESULTS: Social capital, collective efficacy, as well as religious involvement were each significantly associated with middle age mortality. After education, collective efficacy showed the strongest association with mortality in both men and women. Among men, socioeconomic status, collective efficacy, social distrust, competitive attitude, reciprocity, and membership of civic organisations explained 68.0% of the sub-regional variations in mortality rates. Among women the same variables explained only 29.3% of the variance in mortality rates. Religious involvement was protective among women. CONCLUSION: Collective efficacy and social capital are significant predictors of mortality rates in both men and women across sub-regions of Hungary. Gender differences in the relative importance of social factors may help to explain the differential impact of economic transformation on mortality rates for men and women in Central-Eastern European countries.

It is generally believed that treatments are available to manage irritability in Huntington's disease (HD). However, lack of an evidence base prevents the establishment of treatment guidelines for this symptom. The research literature fails to address behavioral intervention strategies, drug selection, drug dosing, management of inadequate response to a single drug, or preferred drugs when additional behavioral symptoms comorbid to irritability are present. In an effort to inform clinical decision-making we surveyed an international group of experts to address these points. The experts consistently endorsed an antipsychotic drug (APD) as first choice for treatment of urgent and aggressive irritability behaviors. However, there was variation in practice patterns for treating less severe symptoms. Serotonin reuptake inhibitors (SSRIs) were first choice drug treatments by most respondents across all geographic regions. However, APDs were also endorsed as first choice for mild or moderate irritability, more frequently in Europe than in North America and Australia. Antiepileptic mood stabilizers (AEDs) were used by fewer respondents as first choice drug. Perceived efficacy for control of mild or moderate irritability was judged somewhat higher for APDs than SSRIs or AEDs. Benzodiazepines were not used as monotherapy, but frequently as an adjunctive drug in the setting of comorbid anxiety. Though many cited lack of experience with mirtazapine, others familiar with its use in HD chose it as an alternative monotherapy, or as adjunctive therapy if insomnia was a comorbid factor. This report presents survey results, reviews available irritability studies, and lastly proposes an algorithm for the treatment of irritability in HD derived from expert preferences obtained through this survey.

BACKGROUND: In clinical practice, several strategies and pharmacological options are available to treat neuropsychiatric symptoms of Huntington disease (HD). However, there is currently insufficient data for evidence-based guidelines on the management of these common symptoms. OBJECTIVE: We aimed to develop expert-based recommendations regarding the management of agitation, anxiety, apathy, psychosis, and sleep disorders. METHODS: Guideline development was based on a modified Institute of Medicine guideline process that accounted for a lack of evidence base. An international committee of 11 multidisciplinary experts proposed a series of statements regarding the description and management of each symptom. Statement assessment and validation was performed using a web-based survey tool and 84 international HD experts (neurologists and psychiatrists) who assessed the statements and indicated their level of agreement. RESULTS: High-level agreement (≥85% experts strongly agreed or agreed) was reached for 107 of the 110 statements that have been incorporated into the expert-based clinical recommendations presented herein. CONCLUSIONS: Clinical statements to guide the routine management of agitation, anxiety, apathy, psychosis, and sleep disorders in HD have been developed. Although not specifically tested in the HD population, clinical experience has shown that most of the neuropsychiatric symptoms discussed, when considered in isolation are treatable using pharmacologic and non-pharmacologic strategies developed for use in other populations. However, the management of neuropsychiatric symptoms in HD can be complex because neuropsychiatric symptoms often co-exist and treatment decisions should be adapted to cover all symptoms while limiting polypharmacy.