First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

[Aging Brain Care Program from Indianapolis: Transferability to the German healthcare system]. / "Aging Brain Care Program" aus Indianapolis: Übertragbarkeit auf den deutschen Versorgungskontext.

BACKGROUND: New and innovative concepts of care management have been developed to improve the health of older adults with dementia and depression. AIM: This article describes the American aging brain care (ABC) program and the possible transfer to the German healthcare system is discussed. MATERIAL AND METHODS: The ABC medical home model in Indianapolis incorporates a specialized geriatric healthcare center which is affiliated to the Eskenazi Hospital as well as a program involving home-based domestic visits by healthcare personnel to affected people. The diagnoses are made in the geriatric center where therapy and treatment are also planned. These stages are carried out in a multiprofessional team, which identifies the individual needs of the patients and relatives and discusses these in family conferences as well as in close consultation with the primary care center of the hospital. The care, diagnosis and therapy are coordinated using a self-developed software for the program and via predetermined pathways and procedural instructions on the approach in the healthcare center and in the domestic visit program. RESULTS AND CONCLUSION: From the perspective of the authors the core elements of the program include not only the use of a home-based care model but also the selection and training of a new type of front-line care provider. Models like the program presented here show great promise for meeting the demands of a rapidly expanding population of vulnerable older adults.

Qualitative needs assessment: healthcare experiences of underserved populations in Montgomery County, Virginia, USA.

INTRODUCTION: Portions of Montgomery County, Virginia, are designated a Medically Underserved Area with a large portion of this population experiencing limited access to healthcare services. In September 2008, the Federal Bureau of Primary Care awarded the authors a planning grant to assess community need in Montgomery County and to develop a strategic plan to establish a Federally Qualified Health Center (FQHC) to best meet these needs. An FQHC is a federally funded clinic mandated to provide medical, dental and mental health services to underserved communities. As part of the planning process, the decision was made to include qualitative data to better understand the needs of underserved residents in the community. Descriptive studies of target populations can provide further insight into community priorities for effective health improvement and planning. The objective of the study was to investigate and describe the perceptions, beliefs and practices that impact healthcare utilization among underserved populations in Montgomery County, Virginia. This study was conducted as part of a comprehensive community assessment to determine the feasibility of developing a FQHC. METHODS: Community focus groups were conducted with target populations which were representative of the community. A thematic analysis of the transcribed field notes and group interviews was conducted. Qualitative data analysis was performed using the Analysis Software for Word-Based Records (AnSWR) developed by the Centers for Disease Control. RESULTS: Three important categories of beliefs which may impact healthcare utilization emerged from the discussions: (1) cultural health perceptions; (2) perceived barriers to care; and (3) coping strategies. Participants expressed a right to access quality care, preferred to spend money on basic living expenses rather than healthcare services; frequently neglected seeking care for adults while rarely neglecting to seek care for their children; valued but infrequently utilized preventative care; and had a lack of confidence in the care that was provided. Perceived barriers to healthcare services reported by participants included a lack of access to affordable care; complexities of health insurance and payer status; limited hours of clinic operation; lack of transportation and geographic distance; and the complexity of navigating the healthcare system. Finally, participants reported using various coping strategies to overcome barriers to accessing healthcare services. These strategies included delaying treatment and self-care; seeking financial and transportation assistance; and using community resources to navigate the system. CONCLUSION: Establishing care that is culturally relevant, targets perceived barriers and incorporates and enhances coping strategies is needed to increase accessibility and utilization of preventative and comprehensive healthcare services. The findings from this study will assist in creating a strategic plan for a FQHC that capitalizes on community strengths while addressing the challenges and complex needs of the community.

Relatedness and social organization of coypus in the Argentinean pampas.

Behavioural and trapping studies of the social organization of coypus have suggested the occurrence of kin groups and a polygynous mating system. We used 16 microsatellite markers to analyse parentage and relatedness relationships in two populations (Jáuregui and Villa Ruiz) in the Argentinean Pampas. At Jáuregui, a dominant male monopolized most paternities, leading to a high variance in reproductive success between males and a high level of polygyny. At Villa Ruiz, variance in reproductive success was low among resident males and males were the fathers of zero to four offspring each. For females, no significant differences were found. Two different social groups in each study site were used to assess genetic relatedness within and between groups. These groups were neighbouring at Jáuregui but not at Villa Ruiz. At Villa Ruiz, coypus were significantly more related within than between groups, suggesting that behavioural groups were also genetic ones, and adult females were more related within than between groups, as should be expected for kin groups. This relationship was not found at Jáuregui. Our results provide support to previous studies based on behavioural and trapping data, which indicate that coypus form social groups and have a polygynous mating system. However, we found differences in social organization between the two populations. This is the first study to determine parentage and/or relatedness in coypus.

A novel trinucleotide repeat expansion at chromosome 3q26.2 identified by a CAG/CTG repeat expansion detection array.

CAG/CTG repeat expansions cause at least 12 different neurological disorders, and additional disorders of this type probably exist. Using the repeat expansion detection (RED) assay, we identified an expanded CAG/CTG repeat in a 50-year-old woman with an autosomal dominant syndrome with prominent progressive sensory neuropathy. The expansion could not be accounted for by any of the CAG/CTG repeats known to undergo expansion. To identify the locus of the expansion, we created a PCR array to assess the repeat length of all repeats of eight or more CAG or CTG triplets in the human genome. The expansion was localized to a repeat contained in an intron of a Genscan-predicted gene, 185 nt downstream of a predicted exon that is conserved through mouse. The closest experimentally verified gene in the region (TNIK, encoding a serine/threonine kinase) occurs approximately 63 Kb downstream from the repeat. The length of the expansion in the proband is 98 triplets. This repeat is not expanded in the proband's cousin (the only other affected family member for whom DNA is currently available) and no expansions were detected in a set of 230 patients with movement disorders of unknown cause. An expanded allele containing 58 triplets was detected in a single control individual, and no other expansions were detected in a set of 255 controls. The normal repeat length ranges from 5 to 30 triplets, with 8 triplets the most common allele. Our results suggest that this new repeat expansion is probably not the direct cause of the phenotype in the proband. Whether the repeat contributes to the patient's phenotype, or is associated with another phenotype, remains to be determined.

Pursuing integration of performance measures into electronic medical records: beta-adrenergic receptor antagonist medications.

OBJECTIVE: Electronic medical records seldom integrate performance indicators into daily operations. Assessing quality indicators traditionally requires resource intensive chart reviews of small samples. We sought to use an electronic medical record to assess use of beta-adrenergic antagonist medications (beta-blockers) following myocardial infarction, to compare a standardized manual assessment with assessment using electronic medical records, and to discuss potential for future integration of performance indicators into electronic records. DESIGN: Cross-sectional data analysis. SETTING: An urban academic medical center. PARTICIPANTS: US Medicare beneficiaries 65 years of age or older, admitted to hospital with myocardial infarction between 1995 and 1999. MEASUREMENTS AND MAIN RESULTS: Manual chart review was compared with a computer driven assessment of electronic records. Administration of beta-blockers and cases excluded from use of beta-blockers were measured, based on Medicare criteria. Among 4490 older adults, 391 (4%) of 9018 hospital admissions contained codes for myocardial infarction. In 323 (83%) of the 391 hospital admissions, criteria for excluding beta-blockers were met; 235 (60%) were excluded due to heart failure. Of 68 hospital admissions for myocardial infarction that did not meet exclusion criteria, physicians prescribed beta-blockers in 49 (72%) on admission and 42 (62%) at discharge. Compared with manual chart review, electronic review had a sensitivity of 83-100% and led to fewer false negative findings. CONCLUSIONS: An electronic medical records system can be used instead of chart review to measure use of beta-blockers after myocardial infarction. This should lead to integration of real time automated performance measurement into electronic medical records.

An unexpectedly high incidence of Epstein-Barr virus lymphoproliferative disease after CD34+ selected autologous peripheral blood stem cell transplant in neuroblastoma.

The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.

Novel CAG/CTG repeat expansion mutations do not contribute to the genetic risk for most cases of bipolar disorder or schizophrenia.

The possible presence of anticipation in bipolar affective disorder and schizophrenia has led to the hypothesis that repeat expansion mutations could contribute to the genetic etiology of these diseases. Using the repeat expansion detection (RED) assay, we have systematically examined genomic DNA from 100 unrelated probands with schizophrenia and 68 unrelated probands with bipolar affective disorder for the presence of CAG/CTG repeat expansions. Our results show that 28% of the probands with schizophrenia and 30% of probands with bipolar disorder have a CAG/CTG repeat in the expanded range, but that each expansion could be explained by one of three nonpathogenic repeat expansions known to exist in the general population. We conclude that novel CAG/CTG repeat expansions are not a common genetic risk factor for bipolar disorder or schizophrenia.

Protection of chickens after live and inactivated virus vaccination against challenge with nephropathogenic infectious bronchitis virus PA/Wolgemuth/98.

Protection provided by live and inactivated virus vaccination against challenge with the virulent nephropathogenic infectious bronchitis virus (NIBV) strain PA/Wolgemuth/98 was assessed. Vaccinations with combinations of live attenuated strains Massachusetts (Mass) + Connecticut (Conn) or Mass + Arkansas (Ark) were given by eyedrop to 2-wk-old specific-pathogen-free leghorn chickens. After live infectious bronchitis virus (IBV) vaccination, some chickens at 6 wk of age received an injection of either an oil emulsion vaccine containing inactivated IBV strains Mass + Ark or an autogenous vaccine prepared from NIBV PA/Wolgemuth/98. Challenge with PA/Wolgemuth/98 was given via eyedrop at 10 wk of age. Serum IBV enzyme-linked immunosorbent assay antibody geometric mean titers (GMTs) after vaccination with the combinations of live attenuated strains were low, ranging from 184 to 1,354, prior to NIBV challenge at 10 wk of age. Both inactivated vaccines induced an anamnestic response of similar magnitudes with serum GMTs of 6,232-12,241. Assessment of protection following NIBV challenge was based on several criteria virus reisolation from trachea and kidney and renal microscopic pathology and IBV-specific antigen immunohistochemistry (IHC). Live attenuated virus vaccination alone with combinations of strains Mass + Conn or Mass + Ark did not protect the respiratory tract and kidney of chickens after PA/Wolgemuth/98 challenge. Chickens given a live combination vaccination of Mass + Conn and boosted with an inactivated Mass + Ark vaccine were also susceptible to NIBV challenge on the basis of virus isolation from trachea and kidney butshowed protection on the basis of renal microscopic pathology and IHC. Live IBV-primed chickens vaccinated with an autogenous inactivated PA/Wolgemuth/98 vaccine had the highest protection against homologous virulent NIBV challenge on the basis of virus isolation.

Empathy in medical students as related to academic performance, clinical competence and gender.

CONTEXT: Empathy is a major component of a satisfactory doctor-patient relationship and the cultivation of empathy is a learning objective proposed by the Association of American Medical Colleges (AAMC) for all American medical schools. Therefore, it is important to address the measurement of empathy, its development and its correlates in medical schools. OBJECTIVES: We designed this study to test two hypotheses: firstly, that medical students with higher empathy scores would obtain higher ratings of clinical competence in core clinical clerkships; and secondly, that women would obtain higher empathy scores than men. MATERIALS AND SUBJECTS: A 20-item empathy scale developed by the authors (Jefferson Scale of Physician Empathy) was completed by 371 third-year medical students (198 men, 173 women). METHODS: Associations between empathy scores and ratings of clinical competence in six core clerkships, gender, and performance on objective examinations were studied by using t-test, analysis of variance, chi-square and correlation coefficients. RESULTS: Both research hypotheses were confirmed. Empathy scores were associated with ratings of clinical competence and gender, but not with performance in objective examinations such as the Medical College Admission Test (MCAT), and Steps 1 and 2 of the US Medical Licensing Examinations (USMLE). CONCLUSIONS: Empathy scores are associated with ratings of clinical competence and gender. The operational measure of empathy used in this study provides opportunities to further examine educational and clinical correlates of empathy, as well as stability and changes in empathy at different stages of undergraduate and graduate medical education.

A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.

We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.

Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling.

Epithelial organs such as the vertebrate hair control periodic self-renewal by regulating the growth of progenitor cells. Recent studies implicate Sonic hedgehog target gene induction in the growth of multipotent hair follicle epithelium and the development of a variety of hair follicle tumors such as basal cell carcinomas. These studies suggest Sonic hedgehog signaling may regulate progenitor cells in other organs.

A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.

Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.

Cognitive impairment and mortality in older primary care patients.

OBJECTIVE: To assess the impact of cognitive impairment on mortality in older primary care patients after controlling for confounding effects of demographic and comorbid chronic conditions. DESIGN: Prospective cohort study. SETTING: Academic primary care group practice. PARTICIPANTS: Three thousand nine hundred and fifty-seven patients age 60 and older who completed the Short Portable Mental Status Questionnaire (SPMSQ) during routine office visits. MEASUREMENTS: Cognitive impairment measured at baseline using the SPMSQ, demographics, problem drinking, history of smoking, clinical data (including weight, cholesterol level, and serum albumin), and comorbid chronic conditions collected at baseline; survival time measured during the 5 to 7 years after baseline. RESULTS: Eight hundred and eighty-six patients (22.4%) died during the 5 to 7 years of follow-up. Cognitive impairment was categorized as having no impairment (84.3%), mild impairment (10.5%), and moderate-to-severe impairment (5.2%) based on SPMSQ score. Chi-square tests revealed that patients with moderate-to-severe impairment were significantly more likely to die compared with patients with mild impairment (40.8% vs 21.5%) and those with no impairment (40.8% vs 21.4%). No significant difference in crude mortality was found between patients with no impairment and those with mild impairment. After analyzing time to death using the Kaplan-Meier method, patients with moderate-to-severe cognitive impairment were at increased risk of death compared with those with no or mild impairment (Log-rank chi(2) = 55.5; P <.0001). Even in multivariable analyses using Cox proportional hazards to control for confounding factors, compared with those with no impairment, moderately-to-severely impaired patients had an increased risk of death, with a hazard ratio (HR) of 1.70. Increased risk of death was also associated with older age (HR = 1.03 for each year), a history of smoking (HR = 1.48), having a serum albumin level <3.5 g/L (HR = 1.29), and weighing less than 90% of the ideal body weight (HR = 1.98). Outpatient diagnoses associated with increased mortality risk were diabetes mellitus, coronary artery disease, congestive heart failure, cerebrovascular disease, cancer, anemia, and chronic obstructive pulmonary disease (HR range 1.36-1.67). Factors protective of mortality risk included female gender (HR = 0.67) and black race (HR = 0.73). CONCLUSIONS: Moderate-to-severe cognitive impairment is associated with an increased risk of mortality, even after controlling for confounding effects of demographic and clinical characteristics. Mild cognitive impairment is not associated with mortality risk, but a longer follow-up period may be necessary to identify this risk if it exists.

Multidisciplinary education and management program for children with asthma.

A multidisciplinary program for managing asthma in a pediatric population is discussed. A coordinated, multidisciplinary program for managing asthma in children was initiated in November 1997 at a U.S. Army medical center. The program, designed to improve care and decrease hospitalizations for asthma, was pharmacist managed and pulmonologist directed and was implemented by pediatricians. Patient education was provided by a pediatric clinical pharmacist or a nurse case manager; providers also received intensive education. Follow-up occurred at predetermined intervals and included asthma education, discussion of expectations and goals, analysis of metered-dose-inhaler and spacer technique, and assessment of compliance. Between November 1997 and January 1999, 210 inpatients were screened for asthma. One hundred seven were believed to have asthma and received inpatient asthma counseling and teaching. Of these 107 patients, 79 were enrolled in the program and monitored in the ambulatory care setting. Seventy-one (90%) of the 79 program enrollees were not rehospitalized during the ensuing two years. The number of children admitted to the hospital for asthma decreased from 147 in 1997 (a rate of 3.2 per 1000 population) to 93 in 1998 (2.1 per 1000) and to 87 in 1999 (1.9 per 1000). A multidisciplinary approach to the management of children with asthma may reduce hospitalizations of such patients.

Quality improvement research on late life depression in primary care.

BACKGROUND: Two million older Americans suffer from depression annually. Depression causes more functional impairment than many other common medical conditions and older adults have the highest rate of suicide in the United States. Although many of these patients fail to seek or fail to receive care for depression, the majority will be seen in primary care for the treatment of other conditions. OBJECTIVE: To review the health services research on quality improvement for late life depression. METHODS: Qualitative literature review. RESULTS: During the past 30 years, multiple educational and quality improvement interventions have been designed and tested to improve the recognition and treatment of depression in primary care settings. The findings from this large body of health services research suggest that: (1) the outcome of major depression in the usual care of primary care is typically poor; this is particularly true of late life depression; (2) informational support provided to primary care physicians is necessary but insufficient to improve the outcomes of late life depression in primary care; achieving guideline-level therapy requires the substantial participation of an informed and motivated patient working in concert with a health care team and health care system designed to care for chronic conditions; (3) up to 30% of older primary care patients will fail to respond to excellent guideline-level therapy provided in primary care; and (4) the latest quality improvement efforts focus not only on the clinical skills of primary care physicians, but also on patient's self-care and on innovative strategies to improve the system of care. CONCLUSIONS: Late life depression is often a chronic disease and outcomes research demonstrates that quality improvement efforts that focus resources on improving systems of care and the active participation of patients offer the best evidence of improved patient outcomes.

Improving primary care for depression in late life: the design of a multicenter randomized trial.

BACKGROUND: Late life depression can be successfully treated with antidepressant medications or psychotherapy, but few depressed older adults receive effective treatment. RESEARCH DESIGN: A randomized controlled trial of a disease management program for late life depression. SUBJECTS: Approximately 1,750 older adults with major depression or dysthymia are recruited from seven national study sites. INTERVENTION: Half of the subjects are randomly assigned to a collaborative care program where a depression clinical specialist supervised by a psychiatrist and a primary care expert supports the patient's regular primary care provider to treat depression. Intervention services are provided for 12 months using antidepressant medications and Problem Solving Treatment in Primary Care according to a stepped care protocol that varies intervention intensity according to clinical needs. The other half of the subjects are assigned to care as usual. EVALUATION: Subjects are independently assessed at baseline, 3 months, 6 months, 12 months, 18 months, and 24 months. The evaluation assesses the incremental cost-effectiveness of the intervention compared with care as usual. Specific outcomes examined include care for depression, depressive symptoms, health-related quality of life, satisfaction with depression care, health care costs, patient time costs, market and nonmarket productivity, and household income. CONCLUSIONS: The study blends methods from health services and clinical research in an effort to protect internal validity while maximizing the generalizability of results to diverse health care systems. We hope that this study will show the cost-effectiveness of a new model of care for late life depression that can be applied in a range of primary care settings.