Work-related rehabilitation aftercare for patients with musculoskeletal disorders: results of a randomized-controlled multicenter trial.
There is evidence that rehabilitation with a multidisciplinary focus on work-related demands effectively improves work ability and quickens return to work in patients with musculoskeletal disorders. There could be benefits to the transfer of work-related components into rehabilitation aftercare. We examined the effectiveness of an intensified work-related rehabilitation aftercare program compared with standard intensified rehabilitation aftercare in Germany on work ability. We randomly assigned 307 patients with musculoskeletal disorders from 11 rehabilitation centers to an aftercare program with work-related functional capacity training, work-related psychosocial groups, social counseling, relaxation training and exercise therapy (intervention group), or the usual aftercare program consisting of only exercise therapy (control group). The 6-month follow-up questionnaire was completed by 78.5% of patients. There was no statistically relevant between-group difference in follow-up primary (work ability) and secondary outcomes (e.g. health-related quality of life, sick leave duration). Significant improvements were observed within both the intervention and the control groups. Severely disabled participants in the intervention group had better physical functioning and shorter sick leave duration after 6 months compared with severely disabled patients in the control group. A partial replacement of standard exercise therapy by a more work-related therapy does not seem to improve work ability superiorly. Improved aftercare treatment may require a focus on employer participation and involvement within the actual work environment.


A new assay of deoxyriboucleases using as a substrate radioactively labelled DNA bound either directly or through anti-DNA antibodies to plastic depression plates.
A simple and accurate method for the detection of Deoxyribonucleases is described. The DNA substrate (3H-labeled) is bound to DNA-binding sites in the "wells" of plastic depression plates either directly of via anti-DNA antibodies. Following incubation with the appropriate enzyme, the radioactivity released from the wells or left bound to the wells is determined. The method is suitable for enzymes which attack native DNA, single stranded DNA and modified DNA (e.g., u.v.-irradiated) as substrates.


Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution.
We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.


Genetic and environmental determinants of malaria parasite virulence in mosquitoes.
Models of malaria epidemiology and evolution are frequently based on the assumption that vector-parasitic associations are benign. Implicit in this assumption is the supposition that all Plasmodium parasites have an equal and neutral effect on vector survival, and thus that there is no parasite genetic variation for vector virulence. While some data support the assumption of avirulence, there has been no examination of the impact of parasite genetic diversity. We conducted a laboratory study with the rodent malaria parasite, Plasmodium chabaudi and the vector, Anopheles stephensi, to determine whether mosquito mortality varied with parasite genotype (CR and ER clones), infection diversity (single versus mixed genotype) and nutrient availability. Vector mortality varied significantly between parasite genotypes, but the rank order of virulence depended on environmental conditions. In standard conditions, mixed genotype infections were the most virulent but when glucose water was limited, mortality was highest in mosquitoes infected with CR. These genotype-by-environment interactions were repeatable across two experiments and could not be explained by variation in anaemia, gametocytaemia, blood meal size, mosquito body size, infection rate or oocyst burden. Variation in the genetic and environmental determinants of virulence may explain conflicting accounts of Plasmodium pathogenicity to mosquitoes in the malaria literature.


Avoidable causes of cancellation in elective orthopaedic surgery.
As part of an audit of clinical practice in an orthopaedic unit for elective surgery, a study was made of the causes of cancellation of operations. Despite careful liaison with general practitioners, and a booked admission policy, over 6% of patients were cancelled as unsuitable. The results of this study suggest that the number of cancellations on medical grounds would be reduced by closer liaison with general practitioners, and the establishment of preadmission clinics. Ensuring that only consultants book patients for surgery would also reduce the number of cancellations due to incorrect indications for surgery.


Confined flows of a polymer microgel.
In this paper, we probe the influence of confinement on the flows of a polymer microgel, namely Carbopol. We compare its bulk rheological behavior, measured with a rheometer and well described by a Hershel-Bulkley law, to velocity profiles measured in rough microchannels, obtained with a particle tracking velocimetry technique. We show a strong disagreement between the bulk prediction for the velocity profiles and the measured ones in the microchannels. Velocity profiles in confined conditions are successfully analyzed within the framework of a non-local fluidity model introduced recently (J. Goyon et al. Nature, 454, 84 (2008)). This allows to determine a cooperativity length ξ, whose order of magnitude compares with the structure size of the microgel. Moreover, we measure flow curves using a rheometer for different gap conditions and also show that this set of data exhibit a strong effect of the confinement on the measured rheological properties. This is again characterized by a typical length of the same order as the cooperativity length scale ξ. We thus evidence confinement effects with two complementary experiments which both give the same typical length for the rearrangements in the flows.


Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results.
Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure. Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning- and MR imaging-guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery. Seventy-five patients (mean age 61 years, range 38-79 years) underwent unilateral pallidotomy. Significant improvements were observed in the "off' period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total "on" time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 +/- 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect. Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.


Cardiac considerations in the triathlete.
The cardiac adaptation to exercise training produces a variety of adaptations in cardiac size, shape, and function. To further define these changes and to investigate the effects of maximal conditioning, we studied ultraendurance triathletes training for the Hawaii Ironman Triathlon using echocardiography, Doppler ultrasound, and electrocardiography. In this population, the left ventricle (LV) was of normal size but had increased wall thickness and mass. Systolic function was normal and diastolic function was normal or supernormal (increased ratio of rapid to atrial LV filling velocities). The finding of a pattern of concentric hypertrophy was reinforced by a close relationship between submaximal exercise systolic blood pressure and LV mass (r = 0.88). Examination of valvular function by Doppler ultrasound revealed significantly increased prevalences of mitral and tricuspid regurgitation in athletes, with 91% of athletes (vs 38% of controls) having regurgitation detected in at least one cardiac valve. Analysis of athletes using standard electrocardiographic criteria for the detection of left ventricular hypertrophy showed that these criteria did not reliably detect increased mass. However, changes such as marked QRS prolongation and nonvoltage criteria for LV hypertrophy and RV hypertrophy may be useful in separating physiologic from pathologic hypertrophy. Our studies provide additional descriptions of cardiac changes produced by ultraendurance exercise training and suggest that the hemodynamic load imposed by exercise may be a contributing cause to physiologic hypertrophy. Much yet remains to be learned about the cardiac adaptation to exercise training.


Multiple plans and memory performance: results of a randomized controlled trial targeting fruit and vegetable intake.
To test whether forming and memorizing more action plans has larger effects than generating fewer plans. In a randomized controlled trial with five intervention groups and one control group, 478 participants were asked to form one, two, three, four, or five action plans, or to complete questionnaires only (control group). One week later, behavior change was measured and participants of the intervention groups completed a free recall task. Outcome measures are daily intake of fruit and vegetables as well as recall of plans. Fruit and vegetable intake increased with higher numbers of plans, and was significantly larger in groups that formed four (d = 0.36) or five plans (d = 0.48) as compared to controls. The sum of recalled plans reflected the number of generated plans, but was unrelated to behavior change. Generating multiple plans benefits behavior change, but to be implemented they need not be recalled.


Homozygous missense WIPI2 variants cause a congenital disorder of autophagy with neurodevelopmental impairments of variable clinical severity and disease course.
WIPI2 is a member of the human WIPI protein family (seven-bladed b-propeller proteins binding phosphatidylinositols, PROPPINs), which play a pivotal role in autophagy and has been implicated in the pathogenesis of several neurological conditions. The homozygous WIPI2 variant c.745G>A; p.(Val249Met) (NM_015610.4) has recently been associated with a neurodevelopmental disorder in a single family. Using exome sequencing and Sanger segregation analysis, here, two novel homozygous WIPI2 variants [c.551T>G; p.(Val184Gly) and c.724C>T; p.(Arg242Trp) (NM_015610.4)] were identified in four individuals of two consanguineous families. Additionally, follow-up clinical data were sought from the previously reported family. Three non-ambulant affected siblings of the first family harbouring the p.(Val184Gly) missense variant presented with microcephaly, profound global developmental delay/intellectual disability, refractory infantile/childhood-onset epilepsy, progressive tetraplegia with joint contractures and dyskinesia. In contrast, the proband of the second family carrying the p.(Arg242Trp) missense variant, similar to the initially reported WIPI2 cases, presented with a milder phenotype, encompassing moderate intellectual disability, speech and visual impairment, autistic features, and an ataxic gait. Brain MR imaging in five patients showed prominent white matter involvement with a global reduction in volume, posterior corpus callosum hypoplasia, abnormal dentate nuclei and hypoplasia of the inferior cerebellar vermis. To investigate the functional impact of these novel WIPI2 variants, we overexpressed both in WIPI2-knockout HEK293A cells. In comparison to wildtype, expression of the Val166Gly WIPI2b mutant resulted in a deficient rescue of LC3 lipidation whereas Arg224Trp mutant increased LC3 lipidation, in line with the previously reported Val231Met variant. These findings support a dysregulation of the early steps of the autophagy pathway. Collectively, our findings provide evidence that biallelic WIPI2 variants cause a neurodevelopmental disorder of variable severity and disease course. Our report expands the clinical spectrum and establishes WIPI2-related disorder as a congenital disorders of autophagy.


A Novel Neurotoxin Gene ar1b Recombination Enhances the Efficiency of Helicoverpa armigera Nucleopolyhedrovirus as a Pesticide by Inhibiting the Host Larvae Ability to Feed and Grow.
A recombinant Helicoverpa armigera nucleopolyhedrovirus (HearNPV), Ar1b-HearNPV, was constructed and identified as an improved bio-control agent of Helicoverpa armigera larvae. The HearNPV polyhedrin promoter was used to express the insect-specific neurotoxin gene, ar1b, which was originally isolated from the Australian funnel-web spider (Atrax robustus). RT-PCR and Western blotting analysis showed that both the ar1b transcript and protein were produced successfully in Ar1b-HearNPV-infected HzAM1 cells. In order to investigate the influence of foreign gene insertion in HearNPV, including the ar1b gene, chloramphenicol resistance gene, lacZ, kanamycin resistance gene, and the gentamicin resistance gene, two virus strains (HZ8-HearNPV and wt-HearNPV) were used as controls in the cell transfection analysis. As expected, foreign gene insertion had no impact on budded virus production and viral DNA replication. Both optical microscopy and electron microscopy observations indicated that the formation of the occlusion bodies of recombinant virus was similar to wild type virus. The Ar1b-HearNPV-infected H. armigera larvae exhibited paralysis and weight loss before dying. This recombinant virus also showed a 32.87% decrease in LT50 assays compared with the wild type virus. Besides, Ar1b-HearNPV also inhibited host larval growth and diet consumption. This inhibition was still significant in the older instar larvae treated with the recombinant virus. All of these positive properties of this novel recombinant HearNPV provide a further opportunity to develop this virus strain into a commercial product to control the cotton bollworm.


Subclinical hypothyroidism might increase the risk of transient atrial fibrillation after coronary artery bypass grafting.
Some studies have proposed that subclinical hypothyroidism (SCH) has adverse effects on the cardiovascular system, but little is known about the effect on patients undergoing cardiovascular operations. We examined the influence of preoperative SCH on postoperative outcome in patients undergoing coronary artery bypass grafting (CABG). Among patients who underwent CABG between July 2005 and June 2007 at Seoul National University Bundang Hospital, 224 with normal thyroid function and 36 with SCH were enrolled. Preoperative risks and postoperative outcomes were evaluated prospectively without thyroid hormone replacement. There were no significant differences in primary outcomes (major adverse cardiovascular events) and secondary outcomes such as wound problems, mediastinitis, leg infection, respiratory complications, delirium, or reoperation during the same hospitalization. However, patients with SCH had a higher incidence of postoperative atrial fibrillation than those with normal thyroid function after adjustment for age, gender, body mass index, and other independent variables such as emergency operation, the use of cardiopulmonary bypass, combined valvular operation, preoperative creatinine levels, left ventricular systolic dysfunction, and nonuse of beta-blockers (45.5% vs 29%; odds ratio, 2.552; 95% confidence interval, 1.117 to 5.830; p = 0.026). SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.


Development and evaluation of an online educational resource about cancer survivorship for cancer nurses: a mixed-methods sequential study.
Cancer survivorship is recognised globally as a key issue. In spite of the key role played by nurses in survivorship care, there is an identified gap in nurse's knowledge in this area. This study reports on the development and evaluation of an educational resource for nurses working with people affected by cancer. The resource was designed using adult learning principles and includes a variety of learning materials and point of care resources. A mixed-methods sequential exploratory design was used to undertake an evaluation of the programme. This included the use of online surveys and semi-structured interviews with pilot participants. A total of 21 participants completed an online survey and 11 participants completed a telephone interview. Overall, the participants found the Cancer Survivorship resource to be engaging, practical and intuitive. A major theme emerging from the survey and interview data was that the resource was applicable to practice and useful in developing survivorship care plans. Respondents requested additional information be included on the role of various health professionals working in survivorship as well as guidelines on when to make referrals. This study provides evidence that the Cancer Survivorship tool may be a promising vehicle for delivering evidence-based education on survivorship care.


The Northern Territory Medical Program - growing our own in the NT.
The Northern Territory (NT) is characterised by major health inequalities. A high proportion of the population is Indigenous, with poor socioeconomic conditions and a high burden of disease. The small NT population - 1% of the total Australian population - is dispersed over one-sixth of Australia's land mass. Given this very low population density and the geographical isolation of many small communities, access to services is often difficult. Medical workforce recruitment and retention have been persistent problems. Prior to 2011, NT residents who aspired to study medicine had to leave the NT. This was the only Australian state or territory that did not have the capacity for students to complete an entire medical degree within the jurisdiction. This article describes the development, implementation and outcomes of the Northern Territory Medical Program (NTMP), which commenced in Darwin in 2011. This was a major development of the Flinders University distributed program, which aimed to develop the medical workforce for the challenging NT environment. Based on evidence regarding the importance of selection in achieving rural workforce outcomes, and a national priority to graduate more Indigenous Australian doctors, NT residents and Indigenous applicants to the NTMP were prioritised in the selection process. Aspiring doctors would not now have to move interstate to study. The curriculum of Flinders University, based in Adelaide, South Australia, would be contextualised to the NT. The NTMP was developed and implemented in collaboration with Charles Darwin University, the major university in the NT. Some of the lessons learned may be useful to others contemplating the delivery of a distributed program that includes a full medical program in a remote area. These include: Leadership at the highest levels of the university is crucial. Expect faculty turnover and avoid single person vulnerabilities. Actively engage local clinicians. Ensure a strong focus on new or alternative selection processes that are able to predict progression. Provide preparatory skills and support for students, especially Indigenous students, with non-science backgrounds. Appreciate and accommodate the community and family pressures experienced by some Indigenous students. Anticipate that the first pioneering cohort of students will not be typical of future cohorts, and work with them to adapt the curriculum, teaching and selection methods. Whilst exemplary telecommunications are needed, some elements of the curriculum will be able to be delivered far better locally than at the larger campus. Do not underestimate the level of student and staff support required both locally and centrally. Develop a 'network' rather than a 'hub and spoke' model. The network may include multiple dispersed placement sites, requiring infrastructure, staffing and ongoing support. The 'new kid' will mean the 'older sibling' will change for the better and use the small size and agility to explore innovations. Focus on the goals. We wanted to contribute to improved economic, social and health outcomes for NT residents by developing an appropriately prepared medical workforce, thereby eliminating the need to recruit doctors from interstate and overseas, and by graduating more Indigenous doctors - potential medical leaders for Australia. Build your expectation for success based on past successes in innovation. Flinders University was able to build on its experience in developing the first 4-year medical program in Australia.


Evidence-based clinical practice guidelines for prostate cancer: the need for a unified approach.
Clinical practice guidelines are being increasingly recognized as critically important to an evidence-based practice. This article reviews the different approaches used by leading urological organizations to the development of prostate cancer guidelines. It further introduces the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group as a unified approach to guideline development. Clinical guidelines on the management of prostate cancer demonstrate major methodological differences. Most notably, considerable discrepancies with regards to the systems used to grade the quality of the evidence and the strength of recommendation exist. The GRADE approach classifies the quality of evidence as high, moderate, low or very low, according to factors that include study design and execution, and the consistency of the results. It subsequently classifies recommendations as strong or weak, according to the balance between benefits and downsides and the degree of confidence in estimates of the downsides. There is an urgent need to standardize processes used to develop clinical guidelines for the management of patients with prostate cancer by leading urological organizations. Adoption of the GRADE approach would offer considerable rewards in terms of efficiency, guideline credibility and optimal clinical decision-making.


Time series analysis of fine particulate matter and asthma reliever dispensations in populations affected by forest fires.
Several studies have evaluated the association between forest fire smoke and acute exacerbations of respiratory diseases, but few have examined effects on pharmaceutical dispensations. We examine the associations between daily fine particulate matter (PM2.5) and pharmaceutical dispensations for salbutamol in forest fire-affected and non-fire-affected populations in British Columbia (BC), Canada. We estimated PM2.5 exposure for populations in administrative health areas using measurements from central monitors. Remote sensing data on fires were used to classify the populations as fire-affected or non-fire-affected, and to identify extreme fire days. Daily counts of salbutamol dispensations between 2003 and 2010 were extracted from the BC PharmaNet database. We estimated rate ratios (RR) and 95% confidence intervals (CIs) for each population during all fire seasons and on extreme fire days, adjusted for temperature, humidity, and temporal trends. Overall effects for fire-affected and non-fire-affected populations were estimated via meta-regression. Fire season PM2.5 was positively associated with salbutamol dispensations in all fire-affected populations, with a meta-regression RR (95% CI) of 1.06 (1.04-1.07) for a 10 ug/m3 increase. Fire season PM2.5 was not significantly associated with salbutamol dispensations in non-fire-affected populations, with a meta-regression RR of 1.00 (0.98-1.01). On extreme fire days PM2.5 was positively associated with salbutamol dispensations in both population types, with a global meta-regression RR of 1.07 (1.04 - 1.09). Salbutamol dispensations were clearly associated with fire-related PM2.5. Significant associations were observed in smaller populations (range: 8,000 to 170,000 persons, median: 26,000) than those reported previously, suggesting that salbutamol dispensations may be a valuable outcome for public health surveillance during fire events.


Pigeon circoviruses from feral pigeons in Australia demonstrate extensive recombination and genetic admixture with other circoviruses.
Like other avian circovirus species, Pigeon circovirus (PiCV) is known to be genetically diverse with a relatively small circular single-stranded DNA genome of 2 kb that encodes for a capsid protein (Cap) and a replication initiator protein (Rep). Recent paleoviral evidence hints towards a probable Gondwanan origin of avian circoviruses, paralleling the evolution and dispersal of their hosts. Limited availability of PiCV genome sequence data in Australia has hindered phylogeographic studies in this species, so we screened clinically normal rock doves (Columba livia) in regional New South Wales, and demonstrated a high prevalence (76%) of PiCV infection by PCR. We also recovered 12 complete novel PiCV genomes and phylogenetic analyses revealed that PiCV circulating in Australian feral pigeons formed two strongly supported monophyletic clades. One clade resided with PiCV genomes from Poland, Australia, United Kingdom, Belgium, China, and Japan, and another basal clade was more closely related to PiCV genomes from Poland. A novel more distantly-related PiCV rep gene formed a solitary clade with weak posterior support. So we further analysed all selected partial rep gene sequences to demonstrate a likely naturally occurring spillover infection from a passerine circovirus candidate. The findings suggest that there is a high degree of genetic variation within PiCV in Columbiformes with potential greater admixture between avian circoviruses within Australia than previously known. RESEARCH HIGHLIGHTS Confirmed high prevalence rate of PiCV circulating in Australian wild pigeons. Highlighted extensive recombination events within Australian PiCV. Demonstrated a likely naturally occurring spillover infection from a passerine circovirus candidate.


Improving psychosexual knowledge in adolescents with autism spectrum disorder: pilot of the tackling teenage training program.
Previous studies have shown that psychosexual functioning in adolescents with autism spectrum disorder (ASD) is hampered and emphasize the need for a specialized training program tailored to their needs. Therefore, an individual training program was developed; the Tackling Teenage Training (TTT) program. The current pilot study systematically evaluated whether psychosexual knowledge increased after taking part in the TTT program, using a pre- and post-training design in 30 adolescents with ASD (77 % male, mean age = 14.80 years, mean intelligence = 96.96). Psychosexual knowledge increased significantly (pre-training total score: M = 25.74, SD = 6.20; post-training total score: M = 33.52 (SD = 2.78); F(1,29) = 65.20, p < .001). The TTT program may be useful to improve psychosexual knowledge and functioning in adolescents with ASD, yet these findings are preliminary, and a more elaborate controlled trial is needed.


A nursing application of telecommunications. Measurement of satisfaction for patients and providers.
Consumer and provider satisfaction is key to the continued use and expansion of telehealth technology. This pilot study compared satisfaction of providers and patients with wound consultations done in person with those done via real-time interactive video technology. Eleven telehealth consultations with a nurse expert were immediately followed by an in-person consultation with a second nurse expert. Satisfaction questionnaires were administered to patients, referring nurses, and the consultant nurse expert following both the in-person consultation and the telehealth consultation. The referring nurses (100%) were satisfied with both the telehealth and in-person consultations, noting the ability to provide better care for their patients. The patients (55%) were "very satisfied" with the telehealth consultations versus 40% satisfied with the in-person consultations. Difficulty in hearing for the patients was equal in both groups, which resulted in changes in the consultation process. The patients' difficulty in seeing the telehealth consultant was addressed through larger screens and strategic positioning to provide easier viewing for the patient and providers. The telehealth nurse consultant was satisfied overall but had some difficulty communicating. This pilot study helped provide useful information for both the telehealth and in-person consultations.


Activation of transcription factor Nrf-2 and its downstream targets in response to moloney murine leukemia virus ts1-induced thiol depletion and oxidative stress in astrocytes.
The neuroimmunodegenerative syndrome that develops in mice infected with ts1, a mutant of Moloney murine leukemia virus, resembles human AIDS. Both ts1 and human immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes but do not infect neurons. Oxidative stress has been implicated in the neuropathology of AIDS dementia and other neurodegenerative diseases. We report here that ts1 infection of astrocytes (both transformed C1 cells and primary cultures) also induces thiol (i.e., glutathione and cysteine) depletion and reactive oxygen species (ROS) accumulation, events occurring in parallel with viral envelope precursor gPr80(env) accumulation and upregulated expression of endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore, ts1-infected astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf-2 transcription factor, as well its targets, the xCT cystine/glutamate antiporter, gamma-glutamylcysteine ligase, and glutathione peroxidase. Depleting intracellular thiols by treating uninfected astrocytes with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine-deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in astrocytes specifically increases expression of the above thiol synthesis-related proteins. Further treatment with BSO or N-acetylcysteine in transfected cells modulates this expression. Thiol depletion also accelerates cell death, while thiol supplementation promotes survival of ts1-infected cells. Together, our results indicate that ts1 infection of astrocytes, along with ts1-induced gPr80(env) accumulation, endoplasmic reticulum stress, thiol depletion, and oxidative stress, accelerates cell death; in response to the thiol depletion and oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant defenses, promoting cell survival.


Production of long chain alcohols and alkanes upon coexpression of an acyl-ACP reductase and aldehyde-deformylating oxygenase with a bacterial type-I fatty acid synthase in E. coli.
Microbial long chain alcohols and alkanes are renewable biofuels that could one day replace petroleum-derived fuels. Here we report a novel pathway for high efficiency production of these products in Escherichia coli strain BL21(DE3). We first identified the acyl-ACP reductase/aldehyde deformylase combinations with the highest activity in this strain. Next, we used catalase coexpression to remove toxic byproducts and increase the overall titer. Finally, by introducing the type-I fatty acid synthase from Corynebacterium ammoniagenes, we were able to bypass host regulatory mechanisms of fatty acid synthesis that have thus far hampered efforts to optimize the yield of acyl-ACP-derived products in BL21(DE3). When all these engineering strategies were combined with subsequent optimization of fermentation conditions, we were able to achieve a final titer around 100 mg L(-1) long chain alcohol/alkane products including a 57 mg L(-1) titer of pentadecane, the highest titer reported in E. coli BL21(DE3) to date. The expression of prokaryotic type-I fatty acid synthases offer a unique strategy to produce fatty acid-derived products in E. coli that does not rely exclusively on the endogenous type-II fatty acid synthase system.


Natural abundance (14)N and (15)N solid-state NMR of pharmaceuticals and their polymorphs.
(14)N ultra-wideline (UW), (1)H{(15)N} indirectly-detected HETCOR (idHETCOR) and (15)N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of (14)N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. A case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW (14)N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR'R''NH(+) and RR'NH2(+)) or other (i.e., RNH2 and RNO2) nitrogen environments. Directly-excited (14)N NMR spectra were acquired using the WURST-CPMG pulse sequence, which incorporates WURST (wideband, uniform rate, and smooth truncation) pulses and a CPMG (Carr-Purcell Meiboom-Gill) refocusing protocol. In certain cases, spectra were acquired using (1)H → (14)N broadband cross-polarization, via the BRAIN-CP (broadband adiabatic inversion - cross polarization) pulse sequence. These spectra provide (14)N electric field gradient (EFG) tensor parameters and orientations that are particularly sensitive to variations in local structure and intermolecular hydrogen-bonding interactions. The (1)H{(15)N} idHETCOR spectra, acquired under conditions of fast magic-angle spinning (MAS), used CP transfers to provide (1)H-(15)N chemical shift correlations for all nitrogen environments, except for two sites in acebutolol and nicardipine. One of these two sites (RR'NH2(+) in acebutolol) was successfully detected using the DNP-enhanced (15)N{(1)H} CP/MAS measurement, and one (RNO2 in nicardipine) remained elusive due to the absence of nearby protons. This exploratory study suggests that this combination of techniques has great potential for the characterization of solid APIs and numerous other organic, biological, and inorganic systems.


A Game-Theoretical Winner and Loser Model of Dominance Hierarchy Formation.
Many animals spend large parts of their lives in groups. Within such groups, they need to find efficient ways of dividing available resources between them. This is often achieved by means of a dominance hierarchy, which in its most extreme linear form allocates a strict priority order to the individuals. Once a hierarchy is formed, it is often stable over long periods, but the formation of hierarchies among individuals with little or no knowledge of each other can involve aggressive contests. The outcome of such contests can have significant effects on later contests, with previous winners more likely to win (winner effects) and previous losers more likely to lose (loser effects). This scenario has been modelled by a number of authors, in particular by Dugatkin. In his model, individuals engage in aggressive contests if the assessment of their fighting ability relative to their opponent is above a threshold [Formula: see text]. Here we present a model where each individual can choose its own value [Formula: see text]. This enables us to address questions such as how aggressive should individuals be in order to take up one of the first places in the hierarchy? We find that a unique strategy evolves, as opposed to a mixture of strategies. Thus, in any scenario there exists a unique best level of aggression, and individuals should not switch between strategies. We find that for optimal strategy choice, the hierarchy forms quickly, after which there are no mutually aggressive contests.


Characterization and calibration of ultraviolet broadband radiometers measuring erythemally weighted irradiance.
An ultraviolet calibration center has been established in Davos, Switzerland. It provides a laboratory for characterizing the spectral and angular response of broadband radiometers. The absolute calibration of these instruments is performed through the comparison to the reference spectroradiometer QASUME. We present what we believe to be a novel calibration methodology that explicitly includes the information of the angular and spectral response functions. From the results of the latest broadband intercomparison campaign, the typical uncertainties of these instruments could be obtained. Most radiometers have an expanded uncertainty of approximately 7%. The angular response introduces an uncertainty of 0.9%-7.2%, depending on the cosine error of the radiometer.


Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial.
To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery. Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity. In this double-blind noninferiority trial, adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively, for 7 to 10 days. Patients underwent bilateral leg venography between 7 and 11 days postsurgery. The primary efficacy end point was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death. The primary safety outcome was bleeding. Both were independently adjudicated. In total, 4413 patients were randomized; 3030 (1499 in the enoxaparin and 1531 in the semuloparin groups) were evaluable for the primary efficacy end point, which occurred in 97 patients (6.3%) in the semuloparin group and 82 patients (5.5%) in the enoxaparin group [odds ratio (OR) = 1.16, 95% confidence interval (CI): 0.84-1.59]. On the basis of a noninferiority margin of 1.25, postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin. Major bleeding occurred in 63 of 2175 patients (2.9%) in the semuloparin group and 98 of 2177 patients (4.5%) in the enoxaparin group (OR = 0.63, 95% CI: 0.46-0.87). Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.


Reorganization of finger coordination patterns during adaptation to rotation and scaling of a newly learned sensorimotor transformation.
We examined how people organize redundant kinematic control variables (finger joint configurations) while learning to make goal-directed movements of a virtual object (a cursor) within a low-dimensional task space (a computer screen). Subjects participated in three experiments performed on separate days. Learning progressed rapidly on day 1, resulting in reduced target capture error and increased cursor trajectory linearity. On days 2 and 3, one group of subjects adapted to a rotation of the nominal map, imposed either stepwise or randomly over trials. Another group experienced a scaling distortion. We report two findings. First, adaptation rates and memory-dependent motor command updating depended on distortion type. Stepwise application and removal of the rotation induced a marked increase in finger motion variability but scaling did not, suggesting that the rotation initiated a more exhaustive search through the space of viable finger motions to resolve the target capture task than did scaling. Indeed, subjects formed new coordination patterns in compensating the rotation but relied on patterns established during baseline practice to compensate the scaling. These findings support the idea that the brain compensates direction and extent errors separately and in computationally distinct ways, but are inconsistent with the idea that once a task is learned, command updating is limited to those degrees of freedom contributing to performance (thereby minimizing energetic or similar costs of control). Second, we report that subjects who learned a scaling while moving to just one target generalized more narrowly across directions than those who learned a rotation. This contrasts with results from whole-arm reaching studies, where a learned scaling generalizes more broadly across direction than rotation. Based on inverse- and forward-dynamics analyses of reaching with the arm, we propose the difference in results derives from extensive exposure in reaching with familiar arm dynamics versus the novelty of the manual task.


The ECG made easy for the dental practitioner.
ECG is not taught to dental students formally in the dental curriculum. The general assumption is that dental surgeons do not handle any ECG related cases in clinical practice. But with an increase in medically compromised patients, the need for an interdisciplinary approach among dental and medical practitioners in the treatment of critically ill patients is becoming more relevant. Hence, we have to be aware of the basics of common medical investigations to be competent to assess and comprehend the medical conditions. So, this paper focuses on orienting the beginner to the basic concepts of ECG from the clinical perspective. The paper also discusses the ECG changes of myocardial infarction to familiarize the dental surgeon to read the ECG.


Glucosamine supplementation after anterior cruciate ligament reconstruction in athletes: a randomized placebo-controlled trial.
Although glucosamine is commonly consumed by athletes, its effectiveness in sports injuries is still under debate. We aimed to investigate the effects of glucosamine to the rehabilitation outcomes of anterior cruciate ligament (ACL) reconstructed athletes. Glucosamine-sulfate (1000 mg daily, for 8 weeks) was administered to half of the cohort of 30 male athletes, the other half used a placebo. Both groups received the same rehabilitation protocol. Knee pain and functions were evaluated by a visual analogue scale (VAS), International Knee Documentation Committee (IKDC) and Lysholm scores before and after oral administration. Additionally, an isokinetic test was performed after the administration period. The scores revealed significant improvements in both groups after 8 weeks, but no significant difference was detected between groups in any of the parameters. Glucosamine supplementation did not improve the rehabilitation outcomes of athletes after ACL reconstruction. This is the first study investigating this topic. Further studies will help to obtain clear evidence about glucosamine efficacy on ACL injured or ACL reconstructed athletes.


Methicillin-resistant Staphylococcus aureus in community-acquired pyoderma.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen. It can also cause community-acquired infections. Indian reports about MRSA in community-acquired infections are rare. To evaluate the rate of MRSA in community-acquired pyoderma and the nasal colonisation with S. aureus in such patients. Two hundred and fifty patients with community-acquired pyoderma, who attended outreach camps around Mangalore, south India between January 2000 and July 2001, were studied. Swabs collected from the skin lesions and anterior nares were inoculated onto blood agar and MacConkey's agar. Antimicrobial sensitivity testing was performed using Kirby-Bauer disk diffusion, agar dilution, and agar screen. Of 250 pyoderma cases, S. aureus was isolated from 202 (80.8%) patients. Twenty-two (10.9%) S. aureus isolates were methicillin resistant, 179 (88.6%) were resistant to penicillin, and 114 (56.4%) were resistant to erythromycin. S. aureus colonization in the anterior nares was observed in 136 (54.4%) cases, 11.8% of which were MRSA. Antibiograms of clinical isolates of S. aureus matched with nasal isolates in 99 (49%) cases. The emergence of MRSA in the community is a warning. A high nasal carriage rate may contribute to recurrent pyoderma. A correct antimicrobial policy and the avoidance of inappropriate antimicrobial usage are mandatory to reduce the spread of MRSA in the community.


Immunocytochemical study of nerve fibers containing substance P in the junctional epithelium of rats.
Nerve fibers with substance P-like immunoreactivity (SP-IR) in the junctional epithelium (JE) of 32-42-d-old rats were examined by both light and electron microscopy using the avidin-biotin-peroxidase complex method. The density of nerve fibers with SP-IR was highest in the middle portion of the JE; however, a few fibers were localized in the coronal portion of the JE and close to the enamel surface. Also, rich innervation was found especially in the basal cell layer of the JE. Unmyelinated axons with SP-IR in the connective tissue underlying the JE were enveloped by Schwann cells but lost their Schwann cell sheath almost completely in the JE. The axons often formed varicosities with SP-IR as terminals in various areas of the JE. The terminals contained numerous large granular vesicles, small clear vesicles and a few mitochondria, and were surrounded by the cytoplasmic processes of the junctional epithelial cells. These terminals were sometimes located close to neutrophils in the JE; the minimum gap distance between the terminals and the processes of junctional epithelial cells or neutrophils was about 20 nm. A few terminals with SP-IR came close to the enamel surface, and the minimal distance between the terminals and the enamel surface was about 5 microns. SP-IR in the nerve terminals in the JE fixed with 0.1% or 0.25% glutaraldehyde was distributed diffusely in the axoplasm or was confined to the granular vesicles. These findings show that substance P is contained in the large granular vesicles in the nerve terminals, and suggest that these terminals may function as modulators of junctional epithelial cells and neutrophils.


Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse.
Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse. Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy. Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission. We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.


What is the place of clinicians' religious or spiritual commitments in psychotherapy? A virtues-based perspective.
Value neutrality in psychotherapy is widely acknowledged to be a myth, and a majority of US physicians report that their religious faith influences their practice. Most attention to therapists' religious and spiritual commitments has focused on ethical boundaries, transference/countertransference dynamics and questions about how to relate religious and psychological truth. No consensus exists about the legitimate place in psychotherapy of clinicians' differing value commitments. Therapists' virtues are vitally important in psychotherapy, not least in the relational and aspirational process by which the patient identifies with the therapist as they engage together in confronting obstacles which the patient has been unable to surmount alone. Among the individual and cultural factors that shape a therapist's virtues are spiritual traditions, which encourage preferred or characteristic virtues. Arguably, these include for Jews, communal responsibility and critical thought; for Christians, love and grace; for Muslims, reverence and obedience; for Buddhists, equanimity and compassion; for Hindus, appreciation of Dharma and Karma; and for secularists, respect for scientific evidence and intelligibility. These have differing implications for treatment, as illustrated through the use of a hypothetical case. Attention to differing spiritual and religious virtues in a pluralistic culture offers opportunities for creative dialogue, collaborative teaching and interdisciplinary research.


Data sets on pensions and health: Data collection and sharing for policy design.
A growing number of countries are developing or reforming pension and health policies in response to population ageing and to enhance the welfare of their citizens. The adoption of different policies by different countries has resulted in several natural experiments. These offer unusual opportunities to examine the effects of varying policies on health and retirement, individual and family behaviour, and well-being. Realizing these opportunities requires harmonized data-collection efforts. An increasing number of countries have agreed to provide data harmonized with the Health and Retirement Study in the United States. This article discusses these data sets, including their key parameters of pension and health status, research designs, samples, and response rates. It also discusses the opportunities they offer for cross-national studies and their implications for policy evaluation and development.


Bacterial natural products in the fight against mosquito-transmitted tropical diseases.
Covering: up to 2019 Secondary metabolites of microbial origin have long been acknowledged as medically relevant, but their full potential remains largely unexploited. Of the countless natural compounds discovered thus far, only 5-10% have been isolated from microorganisms. At the same time, while whole-genome sequencing has demonstrated that bacteria and fungi often encode natural products, only a few genera have yet been mined for new compounds. This review explores the contributions of bacterial natural products to combatting infection by malaria parasites, filarial worms, and arboviruses such as dengue, Zika, Chikungunya, and West Nile. It highlights how molecules isolated from microorganisms ranging from marine cyanobacteria to mosquito endosymbionts can be exploited as antimicrobials and antivirals. Pursuit of this mostly untapped source of chemical entities will potentially result in new interventions against these tropical diseases, which are urgently needed to combat the increase in the incidence of resistance.


Early and late response of Nematostella vectensis transcriptome to heavy metals.
Environmental contamination from heavy metals poses a global concern for the marine environment, as heavy metals are passed up the food chain and persist in the environment long after the pollution source is contained. Cnidarians play an important role in shaping marine ecosystems, but environmental pollution profoundly affects their vitality. Among the cnidarians, the sea anemone Nematostella vectensis is an advantageous model for addressing questions in molecular ecology and toxicology as it tolerates extreme environments and its genome has been published. Here, we employed a transcriptome-wide RNA-Seq approach to analyse N. vectensis molecular defence mechanisms against four heavy metals: Hg, Cu, Cd and Zn. Altogether, more than 4800 transcripts showed significant changes in gene expression. Hg had the greatest impact on up-regulating transcripts, followed by Cu, Zn and Cd. We identified, for the first time in Cnidaria, co-up-regulation of immediate-early transcription factors such as Egr1, AP1 and NF-κB. Time-course analysis of these genes revealed their early expression as rapidly as one hour after exposure to heavy metals, suggesting that they may complement or substitute for the roles of the metal-mediating Mtf1 transcription factor. We further characterized the regulation of a large array of stress-response gene families, including Hsp, ABC, CYP members and phytochelatin synthase, that may regulate synthesis of the metal-binding phytochelatins instead of the metallothioneins that are absent from Cnidaria genome. This study provides mechanistic insight into heavy metal toxicity in N. vectensis and sheds light on ancestral stress adaptations.


Perceived trajectories of life satisfaction across past, present, and future: profiles and correlates of subjective change in young, middle-aged, and older adults.
Despite longitudinal stability in subjective well-being across adulthood, many adults perceive self-related change. This study was aimed at identifying differential subjective change profiles in life satisfaction rated for the present, the past, and the future and to examine their associations with sociodemographic variables and changes in adaptive functioning. The authors addressed this aim using Midlife in the United States survey data from 2 measurement occasions (N=3,631; age at Time 1: 24-75). A cluster analysis was used to identify a continuous high subgroup and an incremental subgroup at both occasions. A 3rd subgroup was labeled present low at Time 1 and decremental at Time 2. Although the average pattern across individual variables suggested stability, up to 60% of individuals fit profiles depicting perceived change, and some individuals changed subgroup membership over time. After controlling for sociodemographic characteristics, subgroups differed in level and change in biopsychosocial measures of adaptive functioning, with sense of control and social relationship quality showing stronger associations than personality and physical health. Results indicate that a person-centered approach to assessing life satisfaction provides a rich and dynamic picture of individual differences in subjective well-being across the adult life span.


Design and Validation of an Instrumented Uneven Terrain Treadmill.
Studying human and animal locomotion on an uneven terrain can be beneficial to basic science and applied studies for clinical and robotic applications. Traditional biomechanical analysis of human locomotion has often been limited to laboratory environments with flat, smooth runways and treadmills. The authors modified a regular exercise treadmill by attaching wooden blocks to the treadmill belt to yield an uneven locomotion surface. To ensure that these treadmill modifications facilitated biomechanical measurements, the authors compared ground reaction force data collected while a subject ran on the modified instrumented treadmill with a smooth surface with data collected using a conventional instrumented treadmill. Comparisons showed only minor differences. These results suggest that adding an uneven surface to a modified treadmill is a viable option for studying human or animal locomotion on an uneven terrain. Other types of surfaces (eg, compliant blocks) could be affixed in a similar manner for studies on other types of locomotion surfaces.


Global justice and health systems research in low- and middle-income countries.
Scholarship focusing on how international research can contribute to justice in global health has primarily explored requirements for the conduct of clinical trials. Yet health systems research in low- and middle-income countries (LMICs) has increasingly been identified as vital to the reduction of health disparities between and within countries. This paper expands an existing ethical framework based on the health capability paradigm - research for health justice - to externally-funded health systems research in LMICs. It argues that a specific form of health systems research in LMICs is required if the enterprise is to advance global health equity. "Research for health justice" requirements for priority setting, research capacity strengthening, and post-study benefits in health systems research are derived in light of the field's distinctive characteristics. Specific obligations are established for external research actors, including governments, funders, sponsors, and investigators. How these framework requirements differ from those for international clinical research is discussed.


Biomarker validation of reports of recent sexual activity: results of a randomized controlled study in Zimbabwe.
Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fisher's exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.


Spatial distribution and hatching of overwintered eggs of a fish ectoparasite, Argulus coregoni (Crustacea: Branchiura).
The habitat distribution of overwintered eggs, which were found to be the only source of spring recruitment of Argulus coregoni Thorell, was studied at a commercial fish farm in Central Finland. The frequency of occurrence of egg clutches in the deep parts of the canals and ponds was 50 to 80% and the percentage cover of the surface of stones with egg clutches was 1.7 to 6.4%, while in the shallow parts these values were 8 to 27% and 0.1 to 0.3%, respectively. A greater proportion of empty egg-shells was observed in shallow water in the mid-May, suggesting an earlier hatching there stimulated by the increased temperature and higher illumination. Under laboratory conditions, only elevated UV illumination, but not diurnally fluctuating temperature, significantly accelerated hatching. Normally overwintered eggs produced a pronounced peak of hatched larvae at the end of May and hatching continued at a much slower rate throughout the summer. Eggs that overwintered twice, first normally and then for a second time buried under sediments, were exposed to the same laboratory conditions simultaneously with normally overwintered eggs, but their hatching was delayed until August. The hatching rate was low, but markedly increased in December.


An open access medical knowledge base for community driven diagnostic decision support system development.
While early diagnostic decision support systems were built around knowledge bases, more recent systems employ machine learning to consume large amounts of health data. We argue curated knowledge bases will remain an important component of future diagnostic decision support systems by providing ground truth and facilitating explainable human-computer interaction, but that prototype development is hampered by the lack of freely available computable knowledge bases. We constructed an open access knowledge base and evaluated its potential in the context of a prototype decision support system. We developed a modified set-covering algorithm to benchmark the performance of our knowledge base compared to existing platforms. Testing was based on case reports from selected literature and medical student preparatory material. The knowledge base contains over 2000 ICD-10 coded diseases and 450 RX-Norm coded medications, with over 8000 unique observations encoded as SNOMED or LOINC semantic terms. Using 117 medical cases, we found the accuracy of the knowledge base and test algorithm to be comparable to established diagnostic tools such as Isabel and DXplain. Our prototype, as well as DXplain, showed the correct answer as "best suggestion" in 33% of the cases. While we identified shortcomings during development and evaluation, we found the knowledge base to be a promising platform for decision support systems. We built and successfully evaluated an open access knowledge base to facilitate the development of new medical diagnostic assistants. This knowledge base can be expanded and curated by users and serve as a starting point to facilitate new technology development and system improvement in many contexts.


Tablet computer enhanced training improves internal medicine exam performance.
Traditional teaching concepts in medical education do not take full advantage of current information technology. We aimed to objectively determine the impact of Tablet PC enhanced training on learning experience and MKSAP® (medical knowledge self-assessment program) exam performance. In this single center, prospective, controlled study final year medical students and medical residents doing an inpatient service rotation were alternatingly assigned to either the active test (Tablet PC with custom multimedia education software package) or traditional education (control) group, respectively. All completed an extensive questionnaire to collect their socio-demographic data, evaluate educational status, computer affinity and skills, problem solving, eLearning knowledge and self-rated medical knowledge. Both groups were MKSAP® tested at the beginning and the end of their rotation. The MKSAP® score at the final exam was the primary endpoint. Data of 55 (tablet n = 24, controls n = 31) male 36.4%, median age 28 years, 65.5% students, were evaluable. The mean MKSAP® score improved in the tablet PC (score Δ + 8 SD: 11), but not the control group (score Δ- 7, SD: 11), respectively. After adjustment for baseline score and confounders the Tablet PC group showed on average 11% better MKSAP® test results compared to the control group (p<0.001). The most commonly used resources for medical problem solving were journal articles looked up on PubMed or Google®, and books. Our study provides evidence, that tablet computer based integrated training and clinical practice enhances medical education and exam performance. Larger, multicenter trials are required to independently validate our data. Residency and fellowship directors are encouraged to consider adding portable computer devices, multimedia content and introduce blended learning to their respective training programs.


Electrophysiological correlates of conscious vision: evidence from unilateral extinction.
To study the electrophysiological correlates of conscious vision, we recorded event-related potentials (ERPs) in a patient with partial unilateral visual extinction as a result of right-hemisphere damage. When, following bilateral presentations, contralesional stimuli were not perceived, there was an absence of the early attention-sensitive P1 (80-120 msec) and N1 (140-180 msec) components of the ERP response. In contrast, following unilateral presentations, or in those bilateral presentations in which contralesional stimuli were perceived (about 60%), these ERP components were present. These results provide novel evidence that extinction involves the stage of early focusing of attention and that the P1 and N1 components of visual ERPs are reliable physiological correlates of conscious vision.


Psychological variables and cancer pain.
Pain can cause both physical and psychological distress that has a negative impact on a patient's quality of life. The purpose of this descriptive study was to determine whether cancer patients (N = 60) with pain (n = 30) had higher scores of depression, anxiety, somatization, and hostility than did cancer patients without pain (n = 30). The study was conducted in a midwestern medical center hospital during a 9-month period. Psychological variables were measured using subscales of the Brief Symptom Inventory (BSI). Patients who reported pain completed the McGill Pain Questionnaire (MPQ) and Visual Analogue Scale. Significant positive correlations were found between total MPQ scores and all four subscales of the BSI (r = 0.60-0.78, p < 0.05). Patients with pain scored higher on all four subscales of the BSI, with significant differences occurring in somatization (t = 2.05, p < 0.05) and hostility (t = 1.93, p < 0.05). The findings suggest a relationship between pain intensity and psychological status. Nursing interventions aimed at reducing these factors may help to decrease the pain, in addition to then decreasing the psychological distress experienced by patients with cancer.


Copper Iodide on Spacer Fabrics as Textile Thermoelectric Device for Energy Generation.
The integration of electronic functionalities into textiles for use as wearable sensors, energy harvesters, or coolers has become increasingly important in recent years. A special focus is on efficient thermoelectric materials. Copper iodide as a p-type thermoelectrically active, nontoxic material is attractive for energy harvesting and energy generation because of its transparency and possible high-power factor. The deposition of CuI on polyester spacer fabrics by wet chemical processes represents a great potential for use in textile industry for example as flexible thermoelectric energy generators in the leisure or industrial sector as well as in medical technologies. The deposited material on polyester yarn is investigated by electron microscopy, x-ray diffraction and by thermoelectric measurements. The Seebeck coefficient was observed between 112 and 153 µV/K in a temperature range between 30 °C and 90 °C. It is demonstrated that the maximum output power reached 99 nW at temperature difference of 65.5 K with respect to room temperature for a single textile element. However, several elements can be connected in series and the output power can be linear upscaled. Thus, CuI coated on 3D spacer fabrics can be attractive to fabricate thermoelectric devices especially in the lower temperature range for textile medical or leisure applications.


Reductions in HIV/STI incidence and sharing of injection equipment among female sex workers who inject drugs: results from a randomized controlled trial.
We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs (FSW-IDUs) in Tijuana and Ciudad Juarez, Mexico during 2008-2010, when harm reduction coverage was expanding rapidly in Tijuana, but less so in Juarez. FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a randomized factorial trial comparing four brief, single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use, and an injection risk intervention to reduce sharing of needles/injection paraphernalia. Women underwent quarterly interviews and testing for HIV, syphilis, gonorrhea, Chlamydia and Trichomonas, blinding interviewers and assessors to assignment. Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency. Of 584 initially HIV-negative FSW-IDUs, retention was ≥90%. After 12 months, HIV/STI incidence decreased >50% in the interactive vs. didactic sex intervention (Tijuana:AdjRR:0.38,95% CI:0.16-0.89; Juarez: AdjRR:0.44,95% CI:0.19-0.99). In Juarez, women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85% vs. 71%, respectively (p = 0.04); in Tijuana, receptive needle sharing declined by 95%, but was similar in active versus didactic groups. Tijuana women reported significant increases in access to syringes and condoms, but Juarez women did not. After 12 months in both cities, the interactive sexual risk intervention significantly reduced HIV/STI incidence. Expanding free access to sterile syringes coupled with brief, didactic education on safer injection was necessary and sufficient for achieving robust, sustained injection risk reductions in Tijuana. In the absence of expanding syringe access in Juarez, the injection risk intervention achieved significant, albeit more modest reductions, suggesting that community-level interventions incorporating harm reduction are more powerful than individual-level interventions. clinicaltrials.gov NCT00840658.


Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy.
Influence of household pets in the development of childhood asthma or atopy has been controversial. The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization. This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, and total serum IgE at 9 months, 6 years, and 11 years of age. Children living in households with > or =1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P =.004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P <.001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P =.87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age. Dog exposure in early life might prevent the development of asthma-like symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.


R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling.
R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 and 3 potentiate WNT/β-catenin signaling in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 and 6 (Lebensohn and Rohatgi, 2018). We now show that heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis and ligand engineering. Mutations in RSPO3 residues predicted to contact HSPGs impair its signaling capacity. Conversely, the HSPG-binding domains of RSPO3 can be entirely replaced with an antibody that recognizes heparan sulfate (HS) chains attached to multiple HSPGs without diminishing WNT-potentiating activity in cultured cells and intestinal organoids. A genome-wide screen for mediators of RSPO3 signaling in cells lacking LGRs 4, 5 and 6 failed to reveal other receptors. We conclude that HSPGs are RSPO co-receptors that potentiate WNT signaling in the presence and absence of LGRs.


Cloning and characterization of the choline acetyltransferase structural gene (cha-1) from C. elegans.
We have cloned the cha-1 gene from Caenorhabditis elegans using the method of transposon tagging, cha-1 is the structural gene for ChAT, the enzyme that synthesizes ACh. Sequence analysis of cDNAs predicts a protein of 71.5 kDa; comparison of the deduced amino acid sequence with ChAT sequences from other species confirms that cha-1 encodes ChAT. Comparison of cDNA and genomic sequences reveals that transcription is from right to left on the genetic map, and that some of the transcripts may result from trans-splicing of the 22-base spliced leader SL 1. The cha-1 gene is organized into 11 exons. The first exon contains only untranslated sequences, and is followed by an extremely long intron. The coding sequence of the cha-1 transcript is disrupted by mutations in the cha-1 gene. We have determined the sites of four transposon insertions and the end-points of two deletions that lead to the cha-1 mutant phenotype; one of the deletions appears to eliminate gene function completely. Comparison of the Drosophila, rat, and C. elegans genes reveals conserved motifs and conserved intron sites.


Structural and functional analysis of nanopillar spin electronic devices fabricated by 3D focused ion beam lithography.
We discuss the fabrication of nanopillar spin electronic devices from metal multilayered heterostructures, utilizing a novel three-dimensional focused ion beam lithography process. Finite element simulation was performed to optimize the geometry of the nanopillar device and to demonstrate that current flow is perpendicular to the plane within the active region of the device. Clear zero-field current induced magnetization switching is observed in our nanopillar devices at room temperature.


T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage. Here we showed that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of Treg cell-specific CpG hypomethylation pattern. Both events were induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation began in the thymus and continued to proceed in the periphery and could be fully established without Foxp3. The hypomethylation was required for Foxp3(+) T cells to acquire Treg cell-type gene expression, lineage stability, and full suppressive activity. Thus, those T cells in which the two events have concurrently occurred are developmentally set into the Treg cell lineage. This model explains how Treg cell fate and plasticity is controlled and can be exploited to generate functionally stable Treg cells.


Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome.
Smith-Lemli-Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium.


Gender differences in working memory networks: a BrainMap meta-analysis.
Gender differences in psychological processes have been of great interest in a variety of fields. While the majority of research in this area has focused on specific differences in relation to test performance, this study sought to determine the underlying neurofunctional differences observed during working memory, a pivotal cognitive process shown to be predictive of academic achievement and intelligence. Using the BrainMap database, we performed a meta-analysis and applied activation likelihood estimation to our search set. Our results demonstrate consistent working memory networks across genders, but also provide evidence for gender-specific networks whereby females consistently activate more limbic (e.g., amygdala and hippocampus) and prefrontal structures (e.g., right inferior frontal gyrus), and males activate a distributed network inclusive of more parietal regions. These data provide a framework for future investigations using functional or effective connectivity methods to elucidate the underpinnings of gender differences in neural network recruitment during working memory tasks.


Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus.
The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial, and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus. The DCCT proved that intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment. The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin (HbA(1c)) level over the follow-up period preceding each event. Intensive treatment was most effective when begun early, before complications were detectable. These risk reductions, achieved at a median HbA(1c) level difference of 9.1% for conventional treatment vs 7.3% for intensive treatment have been maintained through 7 years of EDIC, even though the difference in mean HbA(1c) levels of the 2 former randomized treatment groups was only 0.4% at 1 year (P<.001) (8.3% in the former conventional treatment group vs 7.9% in the former intensive treatment group), continued to narrow, and became statistically nonsignificant by 5 years (8.1% vs 8.2%, P =.09). The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group. Thus, the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation. Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter, aiming for a practicable target HbA(1c) level of 7.0% or less.


Electromagnetic analysis of cylindrical invisibility cloaks and the mirage effect.
We present a finite-element analysis of a diffraction problem involving a coated cylinder enabling the electromagnetic cloaking of a lossy object with sharp wedges located within its core. The coating consists of a heterogeneous anisotropic material deduced from a geometrical transformation as first proposed by Pendry [Science 312, 1780 (2006)]. We analyze the electromagnetic response of the cloak in the presence of an electric line source in p polarization and a loop of magnetic current in s polarization. We find that the electromagnetic field radiated by such a source located a fraction of a wavelength from the cloak is perturbed by less than 1%. When the source lies in the coating, it seems to radiate from a shifted location.


General psychopathology, internalising and externalising in children and functional outcomes in late adolescence.
Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact.


Kinetically Stable Single Crystals of Perovskite-Phase CsPbI3.
We use a solid-state method to synthesize single crystals of perovskite-phase cesium lead iodide (γ-CsPbI3) that are kinetically stable at room temperature. Single crystal X-ray diffraction characterization shows the compound is orthorhombic with the GdFeO3 structure at room temperature. Unlike conventional semiconductors, the optical absorption and joint density-of-states of bulk γ-CsPbI3 is greatest near the band edge and decreases beyond the Eg for at least 1.9 eV. Bulk γ-CsPbI3 does not show an excitonic resonance and has an optical band gap of 1.63(3) eV, ∼90 meV smaller than has been reported in thin films; these and other differences indicate that previously measured thin film γ-CsPbI3 shows signatures of quantum confinement. By flowing gases in situ during powder X-ray diffraction measurements, we confirm that γ-CsPbI3 is stable to oxygen but rapidly and catalytically converts to non-perovskite δ-CsPbI3 in the presence of moisture. Our results provide vital parameters for theoretical and experimental investigations into perovskite-phase CsPbI3 that will the guide the design and synthesis of atmospherically stable inorganic halide perovskites.


3D Printing of PDMS Improves Its Mechanical and Cell Adhesion Properties.
Despite extensive use of polydimethylsiloxane (PDMS) in medical applications, such as lab-on-a-chip or tissue/organ-on-a-chip devices, point-of-care devices, and biological machines, the manufacturing of PDMS devices is limited to soft-lithography and its derivatives, which prohibits the fabrication of geometrically complex shapes. With the recent advances in three-dimensional (3D) printing, use of PDMS for fabrication of such complex shapes has gained considerable interest. This research presents a detailed investigation on printability of PDMS elastomers over three concentrations for mechanical and cell adhesion studies. The results demonstrate that 3D printing of PDMS improved the mechanical properties of fabricated samples up to three fold compared to that of cast ones because of the decreased porosity of bubble entrapment. Most importantly, 3D printing facilitates the adhesion of breast cancer cells, whereas cast samples do not allow cellular adhesion without the use of additional coatings such as extracellular matrix proteins. Cells are able to adhere and grow in the grooves along the printed filaments demonstrating that 3D printed devices can be engineered with superior cell adhesion qualities compared to traditionally manufactured PDMS devices.


Prevalence of antibodies to hepatitis E in two rural Egyptian communities.
A population-based serosurvey in two rural Egyptian communities was used to assess age-specific prevalence of antibody to hepatitis E virus (anti-HEV). One community is in the Nile Delta (11,182 inhabitants; 3,997 participants) and the other in Upper Egypt (10,970 inhabitants; 6,029 participants). Samples were tested for anti-HEV with a commercial enzyme-linked immunoassay (ELISA) based on antigens derived from open reading frame (ORF)2 and ORF3. Although there was a clear difference in sensitivity among the lots of the commercial test used, it was still possible to determine the seroprevalence. The seroprevalence of anti-HEV exceeded 60% in the first decade of life, peaked at 76% in the second decade and remained above 60% until the eighth decade. Prevalence of this magnitude is among the highest reported in the world, with an age-specific pattern more similar to hyperendemic hepatitis A virus transmission than generally described. Lot-to-lot variation in the sensitivity of the commercial ELISA kit highlights a problem when comparing seroepidemiologic studies of different populations.


Omethoate modulates some oxidant/antioxidant parameters in frogs (Rana ridibunda Pallas).
The aim of this study was to investigate the effect of an organophosphorus insecticide omethoate (OM), on certain oxidative stress biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT)) in tongue, lung, stomach and muscle tissues of adult frogs (Rana ridibunda Pallas). Animals were exposed to 10 and 20 parts per million dosages of OM for 24, 48, 72 or 96 h. According to the results, MDA level increased significantly in lung and stomach tissues. GSH content fluctuated in lung and muscle while it elevated in tongue and stomach tissues. With regard to antioxidant enzymes (GST, GR and CAT), their activities reduced in tongue, while they increased in lung and fluctuated in stomach and muscle tissues. It can be concluded that exposure of frogs to OM are characterized by increased MDA levels and fluctuated enzyme activities and GSH contents. This may reflect the potential role of these parameters as useful biomarkers for assessment of OM toxicity.


Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities.
Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples. To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States. Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled. Alcohol consumption during pregnancy. Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation. A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children. Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.


The intersections of HIV and violence: directions for future research and interventions.
The purpose of this paper is to review the available literature on the intersections between HIV and violence and present an agenda for future research to guide policy and programs. This paper aims to answer four questions: (1) How does forced sex affect women's risk for HIV infection? (2) How do violence and threats of violence affect women's ability to negotiate condom use? (3) Is the risk of violence greater for women living with HIV infection than for noninfected women? (4) What are the implications of the existing evidence for the direction of future research and interventions? Together this collection of 29 studies from the US and from sub-Saharan Africa provides evidence for several different links between the epidemics of HIV and violence. However, there are a number of methodological limitations that can be overcome with future studies. First, additional prospective studies are needed to describe the ways which violence victimization may increase women's risk for HIV and how being HIV positive affects violence risk. Future studies need to describe men's perspective on both HIV risk and violence in order to develop effective interventions targeting men and women. The definitions and tools for measurement of concepts such as physical violence, forced sex, HIV risk, and serostatus disclosure need to be harmonized in the future. Finally, combining qualitative and quantitative research methods will help to describe the context and scope of the problem. The service implications of these studies are significant. HIV counseling and testing programs offer a unique opportunity to identify and assist women at risk for violence and to identify women who may be at high risk for HIV as a result of their history of assault. In addition, violence prevention programs, in settings where such programs exist, also offer opportunities to counsel women about their risks for sexually transmitted diseases and HIV.


Chronic Obstructive Pulmonary Disease: A 2019 Evidence Analysis Center Evidence-Based Practice Guideline.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder in which patients are at high risk for both pulmonary and systemic complications of their disease. Medical nutrition therapy by a registered dietitian nutritionist can be an integral component of lifestyle treatment targeted at maintaining and improving outcomes, such as lung function, mortality, and quality of life. The Academy of Nutrition and Dietetics (Academy) convened an expert workgroup to conduct a systematic review to update the COPD Evidence-Based Nutrition Practice Guideline. This publication outlines the Academy's Evidence Analysis Library methods used to complete the systematic review and guideline and examines the recommendations and supporting evidence. A total of 14 recommendations were developed based on evidence from eight conclusions. Using the Nutrition Care Process as a framework for practice, recommendations rated as strong included assessing and monitoring and evaluating body weight and medical nutrition therapy by a registered dietitian nutritionist. Weak recommendations included predicting resting and total energy expenditure. All other recommendations were rated as fair. These included individualizing the calorie prescription and macronutrient composition of the diet; assessing and monitoring and evaluating energy intake, serum 25-hydroxyvitamin D levels, and frequency of exacerbations; and determining need for vitamin D supplementation. Fewer than one-third of the systematic review's conclusions could be used to support the recommendations due to conflicting results or limited or no evidence available. The Evidence Analysis Library 2019 COPD Evidence-Based Nutrition Practice Guideline is a valuable resource for registered dietitian nutritionists and other health care professionals caring for those with COPD.


Cross-validation of magnetic resonance elastography and ultrasound-based transient elastography: a preliminary phantom study.
To cross-validate two recent noninvasive elastographic techniques, ultrasound-based transient elastography (UTE) and magnetic resonance elastography (MRE). As potential alternatives to liver biopsy, UTE and MRE are undergoing clinical investigations for liver fibrosis diagnosis and liver disease management around the world. These two techniques use tissue stiffness as a marker for disease state and it is important to do a cross-validation study of both elastographic techniques to determine the consistency with which the two techniques can measure the mechanical properties of materials. In this study, 19 well-characterized phantoms with a range of stiffness values were measured by two clinical devices (a Fibroscan and an MRE system based respectively on the UTE and MRE techniques) successively with the operators double-blinded. Statistical analysis showed that the correlation coefficient was r(2) = 0.93 between MRE and UTE, and there was no evidence of a systematic difference between them within the range of stiffnesses examined. These two noninvasive methods, MRE and UTE, provide clinicians with important new options for improving patient care regarding liver diseases in terms of the diagnosis, prognosis, and monitoring of fibrosis progression, as well for evaluating the efficacy of treatment.