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Behavior problems in children with autism spectrum disorder (ASD) may exacerbate parenting stress. Parenting self-efficacy and family resources may influence this association. We examined cross-sectional statistical mediation effects of parenting self-efficacy on the relationship between child behavior problems and parenting stress and hypothesized that family-level resources moderated this indirect effect. Participants included 132 underserved (Medicaid-eligible) children with ASD (ages 3-13) with racial/ethnic diversity; many (63%) had intellectual disability. Greater externalizing problems were linked with lower parenting self-efficacy, which in turn was associated with increased parenting stress. A larger mediation effect was observed for families with fewer resources. A plausible alternative model (parenting stress mediating parenting self-efficacy) exhibited poorer fit. Implications for family supports and benefits of longitudinal follow-up are discussed., Author(s): Kevin G. Stephenson [sup.1] [sup.2] , Rachel M. Fenning [sup.3] [sup.4] [sup.5] , Eric A. Macklin [sup.6] [sup.7] , Frances Lu [sup.6] , Megan Norris [sup.1] [sup.2] , Robin [...]

A randomized controlled trial established initial efficacy of a novel parent training (PT) intervention for improving oral hygiene and oral health in underserved children with ASD (Fenning et al., 2022 (See CR28)), a population at risk for unmet dental needs. The present study describes our emic approach to PT development alongside treatment outcome data examining feasibility, acceptability, and engagement. Families with Medicaid-eligible children with ASD ages 3 to 13 years (85% male, 62% with intellectual disability) were assigned to receive PT (n = 60) or a psychoeducational toolkit (n = 59). Results indicate strong retention, fidelity, and adherence, with quantitative and qualitative metrics revealing high treatment satisfaction and utilization. Discussion focuses on implications for individualizing treatment to optimize engagement of underrepresented families., Author(s): Rachel M. Fenning [sup.1] [sup.2] [sup.3] , Eric M. Butter [sup.4] [sup.5] , Megan Norris [sup.4] [sup.5] , James Chan [sup.6] , Eric A. Macklin [sup.6] [sup.7] , Kelly [...]

B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and [CD68.sup.+] phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS., Introduction Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the CNS. Multiple molecular mechanisms have been posited as driving lesion pathology (1-3), but the failure to identify [...]

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) throughout many countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating [...]

I. INTRODUCTION It is widely accepted that the United States suffers from a mass incarceration problem. (1) One population within the criminal justice system that receives less attention than incarcerated [...], Alaska's common-law probation system requires that the period of supervision imposed is accompanied by a suspended term of imprisonment. Violation of probation conditions may trigger this suspended term, sending the probationer to prison. Should the probationer complete the entire suspended sentence, he or she is then usually eligible for discharge from probation. In Chinuhuk v. State, the Alaska Supreme Court held that the state legislature had abrogated this traditional scheme with respect to felony sex offenders, replacing it with one that allowed probation to continue although the offenders had completed their suspended terms of imprisonment. This Comment argues that in so doing, the court closed its eyes to any ambiguity in the operative statute, bypassing the rule of lenity's lessons and enforcing a more punitive result than the legislature may have intended to create.

Since establishment of the Global Polio Eradication Initiative (1) in 1988, the number of polio cases worldwide has decreased by >99.9%. Extensive use of live attenuated oral poliovirus vaccine (OPV) [...]

Physiological effects of cellular hypoxia are sensed by prolyl hydroxylase (PHD) enzymes, which regulate HIFs. Genetic interventions on HIF/PHD pathways have revealed multiple phenotypes that extend the known biology of hypoxia. Recent studies have unexpectedly implicated HIF in aspects of multiple immune and inflammatory pathways. However, such studies are often limited by systemic lethal effects and/or use tissue- specific recombination systems, which are inherently irreversible, unphysiologically restricted, and difficult to time. To study these processes better, we developed recombinant mice that expressed tetracycline-regulated shRNAs broadly targeting the main components of the HIF/ PHD pathway, permitting timed bidirectional intervention. We show that stabilization of HIF levels in adult mice through PHD2 enzyme silencing by RNA interference or inducible recombination of floxed alleles results in multilineage leukocytosis and features of autoimmunity. This phenotype was rapidly normalized on reestablishment of the hypoxia-sensing machinery when shRNA expression was discontinued. In both situations, these effects were mediated principally through the Hif2[alpha] isoform. Assessment of cells bearing Treg markers from these mice revealed defective function and proinflammatory effects in vivo. We believe our findings reveal a new role for the PHD2/Hif2[alpha] pathway in the reversible regulation of T cell and immune activity., Introduction HIFs are transcription factors composed of 1 of 3 a chains (HIF1[alpha], Hif2[alpha], and HIF3[alpha]) dimerized to a [beta] chain that mediates the transcriptional response to low oxygen tension [...]

Faith-based and other civil society organizations, along with more ad-hoc groups of Canadians, have sustained a continuous program of private refugee sponsorship in Canada for 40 years. The Syrian refugee exodus inspired thousands of Canadians with little or no prior experience to also take up refugee sponsorship. Little is known about private sponsors, their characteristics and experiences, and the impact of sponsorship on them. This article undertakes two tasks. First, it sketches the contours of a large, interdisciplinary project investigating the phenomenon of private refugee sponsorship from the perspective of Canadian sponsors of Syrians, including both long-term and new sponsors. The project asks how the project of welcoming refugees remakes the citizenship of Canadians. Second, the article presents original data selected from a survey of over 500 sponsors of recently arrived Syrians. We conclude with future directions for research and analysis. Keywords: Refugees, private sponsorship, Syrian refugees, citizenship, Canadian national identity, cosmopolitanism. Au cours des 40 dernieres annees, des organisations religieuses et civiques ainsi que des regroupements citoyens ad hoc ont soutenu un programme continu de parrainage collectif au Canada. Recemment, l'exode syrien a inspire des milliers des canadiens avec peu ou pas d'experience de parrainage collectif a devenir parrains. Jusqu'a present, il existe peu de donnees sur ces personnes, leurs caracteristiques demographiques, leurs motivations et leurs experiences de parrainage collectif. Le present article accomplit deux taches distinctes. Premierement, il decrit les objectifs d'un grand projet interdisciplinaire qui examine l'experience du parrainage collectif du point de vue des parrains canadiens. Le projet cherche a comprendre comment la reception des refugies a influence la perception de la citoyennete canadienne de la part des parrains. Deuxiemement, cet article presente les resultats inedits d'un sondage aupres de plus de 500 parrains de familles syriennes. L'article conclut en identifiant les futures orientations de la recherche. Mots cles : Refugies, parrainage prive, refugies syriens, citoyennete, identite nationale canadienne, cosmopolitisme., INTRODUCTION The Syrian civil war, and the human displacement it precipitated, has reinvigorated domestic and international interest in Canada's unique model of private refugee sponsorship. (1) A fall 2015 federal [...]

I. IntroductionWere one to draw a Venn diagram that put leading administrative law judgments in one circle, and leading migration and citizenship jurisprudence in another, Roncarelli v Duplessis (1) and [...]

Based upon checklist data from the Autism Speaks Autism Treatment Network, we hypothesized that functional constipation (FC) would be associated with rigid-compulsive behavior in children with autism spectrum disorder (ASD). We used the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III to assess FC symptoms in 108 children with ASD. As hypothesized, FC was associated with parent ratings on the Repetitive Behavior Scales-Revised (RBS-R) Compulsive, Ritualistic, and Sameness subscales in the overall population. Of note, FC was less common in children who were not taking medications that target behavior or treat FC. In the medication-free children, rigid-compulsive behavior was not significantly associated with FC. More research is needed to understand the mechanisms underlying these associations., Author(s): Sarah Marler [sup.1] , Bradley J. Ferguson [sup.2] , Evon Batey Lee [sup.3] , Brittany Peters [sup.1] , Kent C. Williams [sup.4] , Erin McDonnell [sup.5] , Eric A. [...]

Background Patients with DNA-damage response genes (DDR)-related pancreas cancer (BRCA1/2 or other DNA-damage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). However, data is scarce pertaining to outcomes in this subset of patients. Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes. Methods Pancreas cancer patients with a germline pathogenic variant in BRCA1/2 or other DDR gene were identified retrospectively through review of medical records (medical genetics/oncology) and genetic testing results at our institution. Data regarding clinical outcomes, therapy received, and survival was subsequently extracted. Results A total of 11 patients with pancreas cancer were identified to carry a pathogenic DDR-variant: BRCA1 (3), ATM (4), BRCA2 (2), PALB2 (1) and FANCC (1). Five of these individuals had prior history of other cancers. Clinically these tumors were localized (4), locally advanced (3), and metastatic (4) at diagnosis. Four out of 11 patients were still alive at time of data review. Survival in the 7 patients who had died was 13.7, 140.0, 20.5, 22.3, 23.5, 25.8, and 111.5 months. All patients with advanced disease had exposure to platinum chemotherapy. Conclusions Historical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors. Keywords: Hereditary cancer, Pancreatic cancer, Platinum chemotherapy, PARP inhibitors, BRCA1/2, Genetic testing, Author(s): Sarah K. Macklin-Mantia[sup.1], Stephanie L. Hines[sup.2] and Pashtoon M. Kasi[sup.3] Background For years, germline testing for hereditary cancer syndromes was completed largely to provide guidance for future surveillance and [...]

Preventing new HIV infection remains a major challenge in our response to the HIV epidemic. A diagnostic assay that could rapidly identify acutely infected individuals who are not yet antibody [...]

Keywords: AXIN2, Hereditary cancer syndrome, Hereditary polyposis, Cancer, Hypodontia, Author(s): Sarah K. Macklin-Mantia[sup.1] and Douglas L. Riegert-Johnson[sup.1,2] To the Editor, We report the case of an AXIN2 pathogenic variant carrier. AXIN2 is a component of the beta catenin destruction [...]

Author(s): Tina Hernandez-Boussard [sup.1] , Paul Macklin [sup.2] , Emily J. Greenspan [sup.3] , Amy L. Gryshuk [sup.4] , Eric Stahlberg [sup.5] , Tanveer Syeda-Mahmood [sup.6] , Ilya Shmulevich [sup.7] [...]

Kim Anderson, Maria Campbell, and Christi Belcourt (eds), Keetsahnak: Our Missing and Murdered Indigenous Sisters (Edmonton: University of Alberta Press, 2018), 400 pp. Paper. $29.95. ISBN 978-1-7721-2367-8. The movement for [...]

Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD., Author(s): Sarah Marler[sup.1] , Bradley J. Ferguson[sup.2] , Evon Batey Lee[sup.3] , Brittany Peters[sup.1] , Kent C. Williams[sup.4] , Erin McDonnell[sup.5] , Eric A. Macklin[sup.5] , Pat Levitt[sup.6] [sup.7] , [...]

Background Genetic testing for hereditary cancer syndromes has been revolutionized by next-generation sequencing, which allows for simultaneous review of numerous genes. Multigene panels are regularly offered to patients because of their scope and decreased cost and turnaround time. However, many genes included on larger panels have not been studied as extensively as BRCA1 and BRCA2 (BRCA1/2), and their clinical effects are often not as well established. Methods We identified patients who received positive test results for pathogenic variants of breast cancer genes from January 2012 through May 2018. We mailed a survey and conducted qualitative interviews to explore the personal and health care experiences of patients with pathogenic variants of BRCA1/2 and patients with 'other' (ie, non-BRCA1/2 or PALB2; PTEN; ATM; TP53; NBM, RAD51C; MSH6) variants. We compared the experiences of these patients. Results Fifty-nine out of 128 individuals responded to the survey (46%). Thirty-two patients had BRCA1/2 variants, and 27 had other variants. (49 women and 10 men; median [range] age, 63 [34-87] years). We interviewed 21 patients (17 women and 4 men; median [range] age, 59.6 [34-82] years). Of the interview participants, ten patients had BRCA1/2 variants, and 11 had non-BRCA1/2 variants. Patients reported receiving poor information about their genetic test results, and they often educated their physicians about their results. Some patients believed that they had been ignored or 'brushed off' by health care professionals because non-BRCA1/2 genes are less understood outside the genetics research community. Patients with BRCA1/2 variants had similar problems with health care providers, despite increased awareness and established guidelines about BRCA1/2. Conclusions Research is required to understand the clinical significance and proper management of diseases attributable to newly characterized hereditary cancer genes. Additional evaluation of patient and provider education should be at the forefront of efforts to improve patient care. Keywords: Familial cancer, Genetic counseling, Genetic risk, Genetics, Hereditary breast cancer, Qualitative research, PALB2, PTEN, ATM, TP53, NBM, RAD51C, MSH6, Author(s): Kristin E. Clift[sup.1], Sarah K. Macklin[sup.2] and Stephanie L. Hines[sup.3] Background Since the 1990s, genetic testing has been offered to patients at high risk for pathogenic variants of the [...]

Preventing new HIV infection remains a major challenge in our response to the HIV epidemic. A diagnostic assay that could rapidly identify acutely infected individuals who are not yet antibody [...]

IV. Citizenship Revocation and the Charter As argued earlier, it would be a contrived and artificial exercise to consider Bill C-24's citizenship revocation scheme in isolation from consequent expulsion. (111) [...]

Since 9/11, Western governments have redefined what it means to be a citizen. Though citizenship is often thought of as an inalienable right, the emergence of the "homegrown " terrorist [...]

Many children with autism spectrum disorders (ASD) have co-occurring feeding problems. However, there is limited knowledge about how these feeding habits are related to other behavioral characteristics ubiqitious in ASD. In a relatively large sample of 256 children with ASD, ages 2-11, we examined the relationships between feeding and mealtime behaviors and social, communication, and cognitive levels as well repetitive and ritualistic behaviors, sensory behaviors, and externalizing and internalizing behaviors. Finally, we examined whether feeding habits were predictive of nutritional adequacy. In this sample, we found strong associations between parent reported feeding habits and (1) repetitive and ritualistic behaviors, (2) sensory features, and (3) externalizing and internalizing behavior. There was a lack of association between feeding behaviors and the social and communication deficits of ASD and cognitive levels. Increases in the degree of problematic feeding behaviors predicted decrements in nutritional adequacy. Keywords Feeding problems * Mealtime behaviors * Nutrition, Introduction Autism spectrum disorders (ASD) are neurodevelopmental disorders that are characterized by deficits in social communication and social interactions, as well as a presence of restricted repetitive and stereotyped patterns [...]

Sex-biased parasitism is found in many species, but the skew to one sex or the other varies and is most likely due to differences in host and parasite behaviour and the intensity of sexual selection. We examined sex-biased parasitism in Richardson's ground squirrels (Urocitellus richardsonii (Sabine, 1822)) and hypothesized that males would be more heavily parasitized than females, as they are larger, have larger home ranges, and display high aggression and fighting during the short mating season, suggesting that they may trade off investment in immunity for higher investment in reproduction. Squirrels were caught during the mating season and examined for endoparasites and ectoparasites. Body mass, condition, and immune measures were recorded. Males had higher nematode prevalence and abundance, whereas females had higher flea prevalence. Males also had lower lymphocytes than females, as well as higher neutrophil to lymphocyte ratios. Females had higher eosinophils and they were in poorer body condition than males. The higher endoparasite loads in males suggests that they may be trading off immunity, whereas higher flea prevalence in females may be due to differences in sociality between the sexes. Our study demonstrates the importance of examining multiple parasite types to understand the factors influencing sex-biased parasitism. Key words: Urocitellus richardsonii, ectoparasites, endoparasites, Richardson's ground squirrels, sex-biased parasitism, immunity. Le parasitisme variant selon le sexe est present chez de nombreuses especes, bien que l'asymetrie vers un sexe plutot que l'autre varie, vraisemblablement en raison de differences de comportement de l'hote et du parasite et de l'intensite de la selection sexuelle. Nous avons examine le parasitisme variant selon le sexe chez les ecureuils de Richardson (Urocitellus richardsonii (Sabine, 1822)) et postule que les males seraient plus intensement parasites que les femelles puisqu'ils sont plus gros, que leurs domaines vitaux sont plus grands et que leur agressivite et leur combativite sont elevees durant la courte periode de rut, laissent croire qu'ils pourraient reduire leur investissement immunitaire au profit d'un investissement accru dans la reproduction. Des ecureuils ont ete captures durant la periode de rut, et leurs endoparasites et ectoparasites ont ete examines. La masse corporelle, l'etat d'embonpoint et des mesures de l'immunite ont ete enregistres. La prevalence et l'abondance de nematodes etaient plus elevees chez les males, alors que la prevalence de puces etait plus grande chez les femelles. Les males avaient egalement moins de lymphocytes que les femelles, ainsi que des rapports neutrophiles:lymphocytes plus eleves. Les femelles avaient plus d'eosinophiles et un moins bon etat d'embonpoint que les males. Les charges d'endoparasites plus elevees des males donnent a penser que ces derniers compromettraient leur immunite au profit d'autres fonctions, alors que la prevalence plus elevee de puces chez les femelles pourrait etre causee par des differences entre les sexes sur le plan de la socialite. Notre etude demontre l'importance d'examiner plusieurs types de parasites pour comprendre les facteurs qui influent sur le parasitisme variant selon le sexe. [Traduit par la Redaction] Mots-cles : Urocitellus richardsonii, ectoparasites, endoparasites, ecureuil de Richardson, parasitisme variant selon le sexe, immunite., Introduction Sex biases in parasite loads are well documented in the literature; however, the sex with the higher parasite loads appears to vary between and even within the species (Krasnov [...]

The length of time that a quantum system can exist in a superposition state is determined by how strongly it interacts with its environment. This interaction entangles the quantum state with the inherent fluctuations of the environment. If these fluctuations are not measured, the environment can be viewed as a source of noise, causing random evolution of the quantum system from an initially pure state into a statistical mixture--a process known as decoherence. However, by accurately measuring the environment in real time, the quantum system can be maintained in a pure state and its time evolution described by a 'quantum trajectory' (1,2) determined by the measurement outcome. Here we use weak measurements to monitor a microwave cavity containing a superconducting quantum bit (qubit), and track the individual quantum trajectories (3) of the system. In this setup, the environment is dominated by the fluctuations of a single electromagnetic mode of the cavity. Using a near-quantum-limited parametric amplifier (4,5), we selectively measure either the phase or the amplitude of the cavity field, and thereby confine trajectories to either the equator or a meridian of the Bloch sphere. We perform quantum state tomography at discrete times along the trajectory to verify that we have faithfully tracked the state of the quantum system as it diffuses on the surface of the Bloch sphere. Our results demonstrate that decoherence can be mitigated by environmental monitoring, and validate the foundation of quantum feedback approaches based on Bayesian statistics (6-8). Moreover, our experiments suggest a new means of implementing 'quantum steering' (9)--the harnessing of action at a distance to manipulate quantum states through measurement., If a quantum system and its environment have a common set of stationary states, then a measurement of the environment ultimately leads to projection of the quantum system onto one [...]

The act of measurement bridges the quantum and classical worlds by projecting a superposition of possible states into a single (probabilistic) outcome. The timescale of this 'instantaneous' process can be [...]

Music has been aptly described as an 'ontological mutant', neither exhaustively captured nor fixed by, yet inextricably related to, its manifestation in performances and notation. This characteristic lends itself to endless debates on its identity as well as to myriad contradictory assessments of its utility and value. While some authors have sought to attribute this phenomenon to the 'experimental' music of the late twentieth century, the present essay points out that impossibility, or rather, its sister concepts irrationality and incommensurability, have been integral to the conception of music since its inception. The shared language of paradox provides a link from the Pythagorean and neo-Platonic consonance through to the fixed ambiguities of contemporary composition. Keywords: Aesthetics; Werktreue; Irrationality; Experimental Music; Milton Babbitt; Pythagoras DOI: 10.1080/07494467.2010.587316

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-8519.2010.01808.x Byline: RUTH MACKLIN (1) Keywords: future of bioethics; history of bioethics; demise of bioethics Abstract: ABSTRACT Fast forward 50 years into the future. A look back at what occurred in the field of bioethics since 2010 reveals that a conference in 2050 commemorated the death of bioethics. In a steady progression over the years, the field became increasingly fragmented and bureaucratized. Disagreement and dissension were rife, and this once flourishing, multidisciplinary field began to splinter in multiple ways. Prominent journals folded, one by one, and were replaced with specialized publications dealing with genethics, reproethics, nanoethics, and necroethics. Mainstream bioethics organizations also collapsed, giving way to new associations along disciplinary and sub-disciplinary lines. Physicians established their own journals, and specialty groups broke away from more general associations of medical ethics. Lawyers also split into three separate factions, and philosophers rejected all but the most rigorous, analytic articles into their newly established journal. Matters finally came to a head with global warming, the world-wide spread of malaria and dengue, and the cost of medical treatments out of reach for almost everyone. The result was the need to develop plans for strict rationing of medical care. At the same time, recognition emerged of the importance of the right to health and the need for global justice in health. By 2060, a spark of hope was ignited, opening the door to the resuscitation of bioethics and involvement of the global community. Author Affiliation: (1)Albert Einstein College of Medicine in the Bronx, New York Article note: Ruth Macklin, PhD, Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Email: ruth.macklin@einstein.yu.edu

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.socscimed.2009.10.024 Byline: Lisa Ann Conboy (a), Eric Macklin (b), John Kelley (c), Efi Kokkotou (d), Anthony Lembo (d), Ted Kaptchuk (a) Abstract: Supportive social relationships, including a positive patient-practitioner relationship, have been associated with positive health outcomes. Using the data from a randomized controlled trial (RCT) undertaken in the Boston area of the United States, this study sought to identify baseline factors predictive of patients' response to an experimentally applied supportive patient-practitioner relationship. To sort through the hundreds of potential attributes affecting the patient-practitioner relationship, we applied a false discovery rate method borrowed from the field of genomics and bioinformatics. To our knowledge such a method has not previously been applied to generate hypotheses from clinical trial data. In a previous RCT, our team investigated the effect of the patient-practitioner relationship on symptom improvement in patients with irritable Bowel syndrome (IBS). Data were collected on a sample of 289 individuals with IBS using a three-week, single blind, three arm, randomized controlled design. We found that a supportive patient-practitioner relationship significantly improved symptomatology and quality of life. A complex, multi-level measurement package was used to prospectively measure change and identify factors associated with improvement. Using a local false discovery rate procedure, we examined the association of 452 baseline subject variables with sensitivity to treatment. Out of 452 variables, only two baseline factors, reclusiveness, and previous trial experience increased sensitivity to the supportive patient-practitioner relationship. A third variable, additional opportunity during the study for subjects to discuss their illness through experiential interview, was associated with improved outcomes among subjects who did not receive the supportive patient-practitioner relationship. The few variables associated with differential benefit suggest that a patient-centered supportive patient-practitioner relationship may be beneficial for most patients. This may be especially important for reclusive individuals. Within the context of our study, additional study attention in the form of repeated experiential interviews compensated for a lack of positive patient-practitioner support. A supportive patient-practitioner relationship may also help overcome low provider expectations for subjects with previous trial experience. These results converge with the results of the parent trial, implicating the importance of the social world in healing. Author Affiliation: (a) Harvard Medical School, Osher Research Center, Boston, MA United States (b) Department of Biostatistics, Massachusetts General Hospital, Boston, MA, United States (c) Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States (d) Department of Gastroenterology, Beth Israel Hospital, Boston, MA, United States Article Note: (footnote) [star] This analysis and research was supported by Samueli Institute for Information Biology. The research was also supported by Grant Number 1K24 AT004095 from the National Center for Complementary and Alternative Medicine (NCCAM), Grant Number 1R01 AT01414-01 from NCCAM and the National Institutes of Digestive, Diabetes and Kidney Disease (NIDDK), Grant Number 1R21 AT002860-01 from NCCAM and the Office of Behavioral and Social Science Research (OBSSR).

Cold, macroscopic mechanical systems are expected to behave contrary to our usual classical understanding of reality; the most striking and counterintuitive predictions involve the existence of states in which the mechanical system is located in two places simultaneously. Various schemes have been proposed to generate and detect such states (1,2), and all require starting from mechanical states that are close to the lowest energy eigenstate, the mechanical ground state. Here we report the cooling of the motion of a radio-frequency nanomechanical resonator by parametric coupling to a driven, microwave-frequency superconducting resonator. Starting from a thermal occupation of 480 quanta, we have observed occupation factors as low as 3.8. ± 1.3 and expect the mechanical resonator to be found with probability 0.21 in the quantum ground state of motion. Further cooling is limited by random excitation of the microwave resonator and heating of the dissipative mechanical bath. This level of cooling is expected to make possible a series of fundamental quantum mechanical observations including direct measurement of the Heisenberg uncertainty principle and quantum entanglement with qubits., Naively treating the motion of a mechanical resonator quantum mechanically produces the elementary result that the energy should be quantized: [E.sub.n] = [[??]ω.sub.m] (n + 1/2), where n is an [...]

Multiple linear regressions (MLRs), generalized additive models (GAMs), and artificial neural networks (ANNs) were compared as methods to forecast recruitment of Gulf of Alaska walleye pollock (Theragra chalcogramma). Each model, based on a conceptual model, was applied to a 41-year time series of recruitment, spawner biomass, and environmental covariates. A subset of the available time series, an in-sample data set consisting of 35 of the 41 data points, was used to fit an environment-dependent recruitment model. Influential covariates were identified through statistical variable selection methods to build the best explanatory recruitment model. An out-of-sample set of six data points was retained for model validation. We tested each model's ability to forecast recruitment by applying them to an out-of-sample data set. For a more robust evaluation of forecast accuracy, models were tested with Monte Carlo resampling trials. The ANNs outperformed the other techniques during the model fitting process. For forecasting, the ANNs were not statistically different from MLRs or GAMS. The results indicated that more complex models tend to be more susceptible to an overparameterization problem. The procedures described in this study show promise for building and testing recruitment forecasting models for other fish species. Nous avons compare les regressions lineaires multiples (MLRs), les modeles additifs generalises (GAMS) et les modeles statistiques de reseaux de neurones artificiels (ANNs) comme methodes pour predire le recrutement de la goberge de (Alaska (Theragra chalcogramma) dans le golfe de (Alaska. Nous avons applique chaque modele, base sur un modele conceptual, a une serie chronologique de 41 annees de donnees sur le recrutement, la biomasse des reproducteurs et les covariables de l'environnement. Un sous-ensemble de la serie chronologique disponible, soft un ensemble de donnees provenant de fechantillon consistant en 35 des 41 points de donnees, a servi a ajuster un modele de recrutement dependent de fenvironnement. Des methodes statistiques de selection des variables ont permis d'identifier les covariables les plus influentes afro de batir le meilleur modele explicatif du recrutement. Un ensemble de six points de donnees hors de fechantillon a ete garde pour la validation des modeles. Nous avons teste la capacite de chaque modele a predire le recrutement en appliquant le modele a un ensemble de donnees hors de l'echantillon. Pour une evaluation plus robuste de la justesse de la prediction, nous avons teste les modeles avec des essais de reechantillonnage de Monte Carlo. Les ANNs surpassent les autres techniques durant le processus d'ajustement des modeles. Pour ce qui est de la prediction, les ANNs ne sont pas statistiquement differents des MLRs et des GAMS. Les resultats indiquent que les modeles plus complexes ont plus tendance a souffrir de problemes de surparametrisation. Les procedures que nous decrivons sont prometteuses pour l'elaboration et fajustement des modeles de prediction du recrutement chez d'autres especes de poisons. [Traduit par la Redaction], Introduction Society is challenged to steward the exploitation of marine resources effectively for the health of the planet. Forecasting recruitment is a commonly recognized, but elusive, goal for the sustainable [...]

The assembly and final installation of the toroidal field (TF) coils in the ITER machine are analyzed. The procedure and tooling required for the TF coils final installation and the feasibility of fulfilling the accuracy needed by the maximum acceptable error fields induced by the TF coils fabrication tolerances and misalignments are analyzed.

A study was conducted to demonstrate how information and communications technology (ICT) literacy skills reflect twenty-first century requirements for researching and communicating information in digital environments. The potential of iSkills, an assessment tool, in determining the effectiveness of instruction programs, is discussed. The findings of the study are also presented.

Background Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome associated with several endocrine as well as non-endocrine tumors and is caused by mutations in the MEN1 gene. Primary hyperparathyroidism affects the majority of MEN1 individuals by age 50 years. Additionally, MEN1 mutations trigger familial isolated hyperparathyroidism. We describe a seemingly unaffected 76-year-old female who presented to our Genetics Clinic with a family history of primary hyperparathyroidism and the identification of a pathogenic MEN1 variant. Case Presentation The patient was a 76 year-old woman who appeared to be unaffected. She had a family history of a known MEN1 pathogenic variant. Molecular testing for the known MEN1 mutation c.1A > G, as well as, biochemical testing, MRI of the brain and abdomen were all performed using standard methods. Molecular testing revealed our patient possessed the MEN1 pathogenic variant previously identified in her two offspring. Physical exam revealed red facial papules with onset in her seventies, involving her cheeks, nose and upper lip. Formerly, she was diagnosed with rosacea by a dermatologist and noted no improvement with treatment. Clinically, these lesions appeared to be facial angiofibromas. Brain MRI was normal. However, an MRI of her abdomen revealed a 1.5 cm lesion at the tail of the pancreas with normal adrenal glands. Glucagon was mildly elevated and pancreatic polypeptide was nearly seven times the upper limit of the normal range. The patient underwent spleen sparing distal pancreatectomy and subsequent pathology was consistent with a well-differentiated pancreatic neuroendocrine tumor (pNET). Conclusions Age-related penetrance and variable expressivity are well documented in families with MEN1. It is thought that nearly all individuals with MEN1 manifest disease by age 40. We present a case of late-onset MEN1 in the absence of the most common feature, primary hyperparathyroidism, but with the presence of a pNET and cutaneous findings. This family expands the phenotype associated with the c.1A > G pathogenic variant and highlights the importance of providing comprehensive assessment of MEN1 mutation carriers in families that at first blush may appear to have isolated hyperparathyroidism., Author(s): Charu Kaiwar[sup.1] , Sarah K. Macklin[sup.2] , Jennifer M. Gass[sup.3,4] , Jessica Jackson[sup.2] , Eric W. Klee[sup.5,6,7] , Stephanie L. Hines[sup.8] , John A. Stauffer[sup.9] and Paldeep S. Atwal[sup.2] [...]