A Novel Health-Transportation Partnership Paves The Road For Young Driver Safety Through Virtual Assessment.
Motor vehicle crashes remain the leading cause of adolescent mortality and injury in the United States. For young drivers, crash risk peaks immediately after licensure and declines during the next two years, making the point of licensure an important safety intervention opportunity. Legislation in Ohio established a unique health-transportation partnership among the State of Ohio, Children's Hospital of Philadelphia, and Diagnostic Driving, Inc., to identify underprepared driver license applicants through a virtual driving assessment system. The system, a computer-based virtual driving test, exposes drivers to common serious crash scenarios to identify critical skill deficits and is delivered in testing centers immediately before the on-road examination. A pilot study of license applicants who completed it showed that the virtual driving assessment system accurately predicted which drivers would fail the on-road examination and provided automated feedback that informed drivers on their skill deficits. At this time, the partnership's work is informing policy changes around integrating the virtual driving assessment system into licensing and driver training with the aim of reducing crashes in the first months of independent driving. The system can be developed to identify deficits in safety-critical skills that lead to crashes in new drivers and to address challenges that the coronavirus disease 2019 pandemic has introduced to driver testing and training.


Truth under a masquerade!
A 32-year-old woman presented with bilateral periorbital oedema of 2 days duration which progressed to proptosis, chemosis with diminution of vision rapidly within a week. She was a known case of adenocarcinoma of the rectum who was treated with surgery and chemotherapy 6 months earlier. Metastasis workup carried out then was negative. On examination, she had bilateral axial proptosis with sluggish pupillary reactions with restricted extra ocular movements. Fundus examination was normal. Systemically, the patient was of poor build and was undernourished. Haemogram showed raised total counts and erythrocyte sedimentation rate. CT orbit and brain showed metastasis to the frontal bones and orbit. On investigating further, the patient had liver and lung metastasis. The patient was started on chemotherapy, but she succumbed to the disease within a week. This case is reported to highlight how bilateral orbital cellulitis can be a presenting sign of systemic metastasis in treated malignancies.


Cognitively Engaging Chronic Physical Activity, But Not Aerobic Exercise, Affects Executive Functions in Primary School Children: A Group-Randomized Controlled Trial.
Although the positive effects of different kinds of physical activity (PA) on cognitive functioning have already been demonstrated in a variety of studies, the role of cognitive engagement in promoting children's executive functions is still unclear. The aim of the current study was therefore to investigate the effects of two qualitatively different chronic PA interventions on executive functions in primary school children. Children (N = 181) aged between 10 and 12 years were assigned to either a 6-week physical education program with a high level of physical exertion and high cognitive engagement (team games), a physical education program with high physical exertion but low cognitive engagement (aerobic exercise), or to a physical education program with both low physical exertion and low cognitive engagement (control condition). Executive functions (updating, inhibition, shifting) and aerobic fitness (multistage 20-m shuttle run test) were measured before and after the respective condition. Results revealed that both interventions (team games and aerobic exercise) have a positive impact on children's aerobic fitness (4-5% increase in estimated VO2max). Importantly, an improvement in shifting performance was found only in the team games and not in the aerobic exercise or control condition. Thus, the inclusion of cognitive engagement in PA seems to be the most promising type of chronic intervention to enhance executive functions in children, providing further evidence for the importance of the qualitative aspects of PA.


Criblamydia sequanensis, a new intracellular Chlamydiales isolated from Seine river water using amoebal co-culture.
Accumulating evidence supports a role for Chlamydia-related organisms as emerging pathogens for human and animals. Assessment of their pathogenicity requires strain availability, at least for animal models and serological studies. As these obligate intracellular species are able to grow inside amoebae, we used co-culture with Acanthamoeba castellanii in an attempt to recover new Chlamydia-related species from river water. We isolated two strains from eight water samples. The first strain is a new Parachlamydia acanthamoebae strain that differs from previously described isolates by only two bases in the complete 16S rRNA gene sequence. The second isolate is the first representative of a new Chlamydiales family, as demonstrated by genetic and phylogenetic analyses of the 16S rRNA, 23S rRNA, ADP/ATP translocase and RnpB encoding genes. Using fluorescent in situ hybridization and electron microscopy, we demonstrated that it grows in high numbers in amoebae, where it exhibits a Chlamydia-like developmental cycle with reticulate bodies and star-like elementary bodies. Based on these results, we propose to name this new species 'Criblamydia sequanensis'. This work confirmed that amoebal co-culture is a relevant method to isolate new chlamydiae, and that it can be successfully applied to ecosystems colonized with a complex microbial community.


Electron trapping on Fe(3+) sites in photodoped ZnO colloidal nanocrystals.
The effects of photodoping on the electronic structure of Fe(3+)-doped ZnO colloidal nanocrystals are presented. We observe disappearance of the spectroscopic signatures attributed to both substitutional Fe(3+) and interstitial Fe(3+) in the ZnO host as a function of photodoping time, which precede the appearance of the well-known localized surface plasmon resonance from conduction band electrons in ZnO nanocrystals. These results suggest that the oxidation state of Fe(3+) defects can be reversibly switched in ZnO nanocrystals.


Visualizing cells and humans in 3D: biomedical image analysis at nanometer and meter scales.
Researchers analyzed and presented volume data from the Visible Human Project (VHP) and data from high-resolution 3D ion-abrasion scanning electron microscopy (IA-SEM). They acquired the VHP data using cryosectioning, a destructive approach to 3D human anatomical imaging resulting in whole-body images with a field of view approaching 2 meters and a minimum resolvable feature size of 300 microns. IA-SEM is a type of block-face imaging microscopy, a destructive approach to microscopic 3D imaging of cells. The field of view of IA-SEM data is on the order of 10 microns (whole cell) with a minimum resolvable feature size of 15 nanometers (single-slice thickness). Despite the difference in subject and scale, the analysis and modeling methods were remarkably similar. They are derived from image processing, computer vision, and computer graphics techniques. Moreover, together we are employing medical illustration, visualization, and rapid prototyping to inform and inspire biomedical science. By combining graphics and biology, we are imaging across nine orders of magnitude of space to better promote public health through research.


Knowledge about emergency dental trauma management among school teachers in Colombia: A baseline study to develop an education strategy.
Dental trauma in school populations has a high frequency and school teachers are often close to the place where such injuries occur. However, many studies have confirmed the lack of knowledge as to how to act in these cases. The aim of this study was to determine the knowledge in regard to dental trauma of school teachers in Colombia. A multicentre, descriptive cross-sectional study was performed in 251 schools using a stratified randomized sampling. A structured hard copy survey was personally delivered to 2390 school teachers in the selected schools. The survey contained questions related to work experience, teaching level and demographic data, as well as questions related to their knowledge of and attitude towards emergency dental trauma management. The response rate was 96%. Most of the school teachers (95%) had never received training related to dental trauma, although 35% had witnessed at least 1 case. Of 2296 school teachers surveyed, only 5.8% would have replanted an avulsed tooth. An association was found between work experience and appropriate management of an avulsed tooth. No significant differences were found in regard to school location (city), school type (private/public), gender and school teachers' education level. The knowledge of school teachers in Colombia about emergency dental trauma management is inadequate. The findings strongly suggest a need for an education strategy with the involvement of the government, dentistry schools and private organizations.


Fluorescent and magnetic anti-counterfeiting realized by biocompatible multifunctional silicon nanoshuttle-based security ink.
Herein, we present the first example of a silicon nanoshuttle-based security ink simultaneously featuring attractive optical and magnetic properties, suitable for fluorescent and magnetic anti-counterfeiting and encryption. Significantly, the information can be dual-encrypted through multi-color fluorescence and longitudinal (T1)/transverse (T2) relaxation contrast by using the silicon nanoshuttle-based security ink. We further demonstrate the feasibility of this high-performance ink for practical application in banknote anti-counterfeiting.


Biosciences in nurse education: is the curriculum fit for practice? Lecturers' views and recommendations from across the UK.
This study aims to review the biosciences component of preregistration nursing programmes in higher education institutions across the UK through the experiences and perceptions of lecturers involved in nursing education. Studies suggest that some qualified nurses lack confidence in explaining the bio-scientific rationale for their clinical practice. Biosciences can be difficult to understand and integrate into clinical decision-making and require protected time within preregistration nurse education. In the absence of explicit national guidelines, it is unclear as to the depth and extent biosciences are taught across different institutions and the level achieved at the point of registration. A survey approach was adopted to generate quantitative and qualitative feedback. Data were collected using a semi-structured questionnaire seeking the experiences and views of lecturers involved in teaching biosciences to nursing students across the UK. Data received from 10 institutions were analysed using descriptive statistics and thematic analysis. Lecturers reported that the hours of taught biosciences ranged from 20-113 hours, principally within the first year. This represents between 0·4-2·4% of time within a preregistration nursing programme (4600 hours). Large group lectures predominate, supplemented by smaller group or practical work, and online materials. The biosciences are assessed specifically in half the institutions surveyed and as part of integrated assessments in the rest. In relation to student feedback, all respondents stated that students consistently requested more time and greater priority for biosciences in their programme. This survey suggests that the number of hours spent teaching biosciences is minimal and varies widely between higher education institutions. All respondents expressed concern about the challenges of teaching difficult bio-scientific concepts to large groups in such a limited time and called for greater clarity in national guidelines to ensure that all nurses are adequately educated and assessed in bioscience subjects. Failure to understand the biosciences underpinning care has implications for safe and competent nursing.


Liver involvement in celiac disease.
Celiac disease is a chronic immune-mediated disorder that may affect several organs. Liver abnormalities are common extraintestinal manifestations of celiac disease. Isolated hypertransaminasemia, with mild or nonspecific histologic changes in the liver biopsy, also known as ''celiac hepatitis'', is the most frequent presentation of liver injury in celiac disease. Both, histologic changes and liver enzymes reverse to normal after treatment with a gluten-free diet in most patients. Celiac disease may also be associated with severe forms of liver disease and/or coexist with other chronic liver disorders (i.e., autoimmune liver diseases). The mechanisms underlying liver injury in celiac disease are poorly understood. Predisposition to autoimmunity by shared genetic factors (i.e., human leukocyte antigen [HLA] genes) as well as the systemic effects of abnormal intestinal permeability, cytokines, autoantibodies, and/or other yet undefined biologic mediators induced by gluten exposure in susceptible persons may play a pathogenic role. The aims of this article are: 1) to review the spectrum of liver injury related to celiac disease and 2) to understand the clinical implications of celiac disease in patients with chronic liver disorders.


Anterior cruciate ligament injury and access to care in South Florida: does insurance status play a role?
Health insurance status and access to care are recurring topics of discussion and concern. The purpose of this investigation was to examine access to care on the basis of insurance status for patients with anterior cruciate ligament (ACL) injuries in South Florida. From March 2010 to March 2011, eighty patients with ACL injuries were identified at a county hospital sports medicine clinic and a university-based sports medicine practice. Demographic and injury-specific data were obtained with attention to the date of injury, the date of diagnosis, and the number of medical visits. Hazard ratios and 95% confidence intervals were calculated from multivariable Cox proportional-hazards regression models to determine the effect of insurance type on the time to diagnosis of an ACL tear. Patients with private insurance were diagnosed at a median fourteen days after the injury, whereas those receiving Medicaid and those without insurance were diagnosed a median of fifty-six and 121 days after the injury, respectively (p < 0.001). Patients without insurance and those receiving Medicaid had more medical visits prior to diagnosis (median, four; range two to six) than those with private insurance (median, three; range, one to five) (p = 0.006). Differences for patient delays due to not seeking care were not significant among the three groups (p = 0.484). When grouped according to insurance status, subjects receiving Medicaid in South Florida faced greater system-related delays in obtaining care than did subjects with private insurance. System-related factors such as lack of access to specialized care result in an increased number of medical encounters. These regional findings are consistent with those of other regional studies on access to orthopaedic care.


S-Adenosylmethionine decarboxylase from the archaeon Methanococcus jannaschii: identification of a novel family of pyruvoyl enzymes.
Polyamines are present in high concentrations in archaea, yet little is known about their synthesis, except by extrapolation from bacterial and eucaryal systems. S-Adenosylmethionine (AdoMet) decarboxylase, a pyruvoyl group-containing enzyme that is required for spermidine biosynthesis, has been previously identified in eucarya and Escherichia coli. Despite spermidine concentrations in the Methanococcales that are several times higher than in E. coli, no AdoMet decarboxylase gene was recognized in the complete genome sequence of Methanococcus jannaschii. The gene encoding AdoMet decarboxylase in this archaeon is identified herein as a highly diverged homolog of the E. coli speD gene (less than 11% identity). The M. jannaschii enzyme has been expressed in E. coli and purified to homogeneity. Mass spectrometry showed that the enzyme is composed of two subunits of 61 and 63 residues that are derived from a common proenzyme; these proteins associate in an (alphabeta)(2) complex. The pyruvoyl-containing subunit is less than one-half the size of that in previously reported AdoMet decarboxylases, but the holoenzyme has enzymatic activity comparable to that of other AdoMet decarboxylases. The sequence of the M. jannaschii enzyme is a prototype of a class of AdoMet decarboxylases that includes homologs in other archaea and diverse bacteria. The broad phylogenetic distribution of this group suggests that the canonical SpeD-type decarboxylase was derived from an archaeal enzyme within the gamma proteobacterial lineage. Both SpeD-type and archaeal-type enzymes have diverged widely in sequence and size from analogous eucaryal enzymes.


Desensitization protocols and their outcome.
In the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.


Nosocomial transmission of human granulocytic anaplasmosis in China.
Human granulocytic anaplasmosis (HGA) is an emerging tick-borne disease in China. A cluster of cases among health care workers and family members following exposure to a patient with fulminant disease consistent with HGA prompted investigation. To investigate the origin and transmission of apparent nosocomial cases of febrile illness in the Anhui Province. After exposure to an index patient whose fatal illness was characterized by fever and hemorrhage at a primary care hospital and regional tertiary care hospital's isolation ward, secondary cases with febrile illness who were suspected of being exposed were tested for antibodies against Anaplasma phagocytophilum and by polymerase chain reaction (PCR) and DNA sequencing for A. phagocytophilum DNA. Potential sources of exposure were investigated. Cases with serological or PCR evidence of HGA were compared with uninfected contacts to define the attack rate, relative risk of illness, and potential risks for exposure during the provision of care to the index patient. In a regional hospital of Anhui Province, China, between November 9 and 17, 2006, a cluster of 9 febrile patients with leukopenia, thrombocytopenia, and elevated serum aminotransferase levels were diagnosed with HGA by PCR for A. phagocytophilum DNA in peripheral blood and by seroconversion to A. phagocytophilum. No patients had tick bites. All 9 patients had contact with the index patient within 12 hours of her death from suspected fatal HGA while she experienced extensive hemorrhage and underwent endotracheal intubation. The attack rate was 32.1% vs 0% (P = .04) among contacts exposed at 50 cm or closer, 45% vs 0% (P = .001) among those exposed for more than 2 hours, 75% vs 0% (P < .001) among those reporting contact with blood secretions, and 87.5% vs 0% (P = .004) among those reporting contact with respiratory secretions from the index patient. We report the identification of HGA in China and likely nosocomial transmission of HGA from direct contact with blood or respiratory secretions.


Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.
With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.


Natural mercury isotope variation in coal deposits and organic soils.
There is a need to distinguish among sources of Hg to the atmosphere in order to more fully understand global Hg pollution. In this study we investigate whether coal deposits within the United States, China, and Russia-Kazakhstan, which are three of the five greatest coal-producing regions, have diagnostic Hg isotopic fingerprints that can be used to discriminate among Hg sources. We also investigate the Hg isotopic composition of modern organic soil horizons developed in areas distant from point sources of Hg in North America. Mercury stored in coal deposits displays a wide range of both mass dependent fractionation (MDF, delta202Hg) and mass independent fractionation (MIF, delta201Hg). delta202Hg varies in coals by 3 per thousand and delta201Hg varies by 0.9 per thousand. Combining these two Hg isotope signals results in what may be a unique isotopic "fingerprint" for many coal deposits. Mass independent fractionation of mercury has been demonstrated to occur during photochemical reactions of mercury. This suggests that Hg found in most coal deposits was subjected to photochemical reduction near the Earth's surface prior to deposition. The similarity in MDF and MIF of modern organic soils and coals from North America suggests that Hg deposition from coal may have imprinted an isotopic signature on soils. This research offers a new tool for characterizing mercury inputs from natural and anthropogenic sources to the atmosphere and provides new insights into the geochemistry of mercury in coal and soils.


The streptococcal binding site in the gelatin-binding domain of fibronectin is consistent with a non-linear arrangement of modules.
Fibronectin-binding proteins (FnBPs) of Staphylococcus aureus and Streptococcus pyogenes mediate invasion of human endothelial and epithelial cells in a process likely to aid the persistence and/or dissemination of infection. In addition to binding sites for the N-terminal domain (NTD) of fibronectin (Fn), a number of streptococcal FnBPs also contain an upstream region (UR) that is closely associated with an NTD-binding region; UR binds to the adjacent gelatin-binding domain (GBD) of Fn. Previously, UR was shown to be required for efficient streptococcal invasion of epithelial cells. Here we show, using a Streptococcus zooepidemicus FnBP, that the UR-binding site in GBD resides largely in the (8)F1(9)F1 module pair. We also show that UR inhibits binding of a peptide from the α1 chain of type I collagen to (8)F1(9)F1 and that UR binding to (8)F1 is likely to occur through anti-parallel β-zipper formation. Thus, we propose that streptococcal proteins that contain adjacent NTD- and GBD-binding sites form a highly unusual extended tandem β-zipper that spans the two domains and mediates high affinity binding to Fn through a large intermolecular interface. The proximity of the UR- and NTD-binding sequences in streptococcal FnBPs is consistent with a non-linear arrangement of modules in the tertiary structure of the GBD of Fn.


Homeless street children in Nepal: use of allostatic load to assess the burden of childhood adversity.
As challenges to child well-being through economic disadvantage, family disruption, and migration or displacement escalate world wide, the need for cross-culturally robust understanding of childhood adversity proportionately increases. Toward this end, developmental risk was assessed in four contrasting groups of 107 Nepali children ages 10-14 years that represent distinctive, common conditions in which contemporary children grow up. Relative cumulative burden (allostatic load) indexed by multiple dimensions of physical and psychosocial stress was ascertained among homeless street boys and three family-based groups, from poor urban squatter settlements, urban middle class, and a remote rural village. Biomarkers of stress and vulnerability to stress included growth status, salivary cortisol, antibodies to Epstein-Barr virus, acute phase inflammatory responses (alpha1-antichymotrypsin), and cardiovascular fitness and reactivity (flex heart rate and pressor response). Individual biomarkers of risk and allostatic load differed markedly among groups, were highest in villagers, and varied by components of allostatic load. Such data suggest a need for critical appraisal of homelessness and migration as a risk factor to youth, given prevailing local conditions such as rural poverty, and represents the only multidimensional study of childhood allostatic load and developmental risk in non-Western settings.


Artificial intelligence framework for simulating clinical decision-making: a Markov decision process approach.
In the modern healthcare system, rapidly expanding costs/complexity, the growing myriad of treatment options, and exploding information streams that often do not effectively reach the front lines hinder the ability to choose optimal treatment decisions over time. The goal in this paper is to develop a general purpose (non-disease-specific) computational/artificial intelligence (AI) framework to address these challenges. This framework serves two potential functions: (1) a simulation environment for exploring various healthcare policies, payment methodologies, etc., and (2) the basis for clinical artificial intelligence - an AI that can "think like a doctor". This approach combines Markov decision processes and dynamic decision networks to learn from clinical data and develop complex plans via simulation of alternative sequential decision paths while capturing the sometimes conflicting, sometimes synergistic interactions of various components in the healthcare system. It can operate in partially observable environments (in the case of missing observations or data) by maintaining belief states about patient health status and functions as an online agent that plans and re-plans as actions are performed and new observations are obtained. This framework was evaluated using real patient data from an electronic health record. The results demonstrate the feasibility of this approach; such an AI framework easily outperforms the current treatment-as-usual (TAU) case-rate/fee-for-service models of healthcare. The cost per unit of outcome change (CPUC) was $189 vs. $497 for AI vs. TAU (where lower is considered optimal) - while at the same time the AI approach could obtain a 30-35% increase in patient outcomes. Tweaking certain AI model parameters could further enhance this advantage, obtaining approximately 50% more improvement (outcome change) for roughly half the costs. Given careful design and problem formulation, an AI simulation framework can approximate optimal decisions even in complex and uncertain environments. Future work is described that outlines potential lines of research and integration of machine learning algorithms for personalized medicine.


Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis.
Spontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes. We performed a retrospective study of 1729 patients with cirrhosis who underwent abdominal computed tomography or magnetic resonance imaging analysis from 2010 through 2015 at 14 centers in Canada and Europe. We collected data on demographic features, etiology of liver disease, comorbidities, complications, treatments, laboratory and clinical parameters, Model for End-Stage Liver Disease (MELD) score, and endoscopy findings. Abdominal images were reviewed by a radiologist (or a hepatologist trained by a radiologist) and searched for the presence of SPSS, defined as spontaneous communications between the portal venous system or splanchnic veins and the systemic venous system, excluding gastroesophageal varices. Patients were assigned to groups with large SPSS (L-SPSS, ≥8 mm), small SPSS (S-SPSS, <8 mm), or without SPSS (W-SPSS). The main outcomes were the incidence of complications of cirrhosis and mortality according to the presence of SPSS. Secondary measurements were the prevalence of SPSS in patients with cirrhosis and their radiologic features. L-SPSS were identified in 488 (28%) patients, S-SPSS in 548 (32%) patients, and no shunt (W-SPSS) in 693 (40%) patients. The most common L-SPSS was splenorenal (46% of L-SPSS). The presence and size of SPSS increased with liver dysfunction: among patients with MELD scores of 6-9, 14% had L-SPSS and 28% had S-SPSS; among patients with MELD scores of 10-13, 30% had L-SPSS and 34% had S-SPSS; among patients with MELD scores of 14 or higher, 40% had L-SPSS and 32% had S-SPSS (P < .001 for multiple comparison among MELD groups). HE was reported in 48% of patients with L-SPSS, 34% of patients with S-SPSS, and 20% of patients W-SPSS (P < .001 for multiple comparison among SPSS groups). Recurrent or persistent HE was reported in 52% of patients with L-SPSS, 44% of patients with S-SPSS, and 37% of patients W-SPSS (P = .007 for multiple comparison among SPSS groups). Patients with SPSS also had a larger number of portal hypertension-related complications (bleeding or ascites) than those W-SPSS. Quality of life and transplantation-free survival were lower in patients with SPSS vs without. SPSS were an independent factor associated with death or liver transplantation (hazard ratio, 1.26; 95% confidence interval, 1.06-1.49) (P = .008) in multivariate analysis. When patients were stratified by MELD score, SPSS were associated with HE independently of liver function: among patients with MELD scores of 6-9, HE was reported in 23% with L-SPSS, 12% with S-SPSS, and 5% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among those with MELD scores of 10-13, HE was reported in 48% with L-SPSS, 33% with S-SPSS, and 23% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among patients with MELD scores of 14 or more, HE was reported in 59% with L-SPSS, 57% with S-SPSS, and 48% with W-SPSS (P = .043 for multiple comparison among SPSS groups). Patients with SPSS and MELD scores of 6-9 were at higher risk for ascites (40.5% vs 23%; P < .001) and bleeding (15% vs 9%; P = .038) than patients W-SPSS and had lower odds of transplant-free survival (hazard ratio 1.71; 95% confidence interval, 1.16-2.51) (P = .006). In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.


A comprehensive examination of the influence of state tobacco control programs and policies on youth smoking.
We examined the influence of tobacco control policies (tobacco control program expenditures, smoke-free air laws, youth access law compliance, and cigarette prices) on youth smoking outcomes (smoking susceptibility, past-year initiation, current smoking, and established smoking). We combined data from the 2002 to 2008 National Surveys on Drug Use and Health with state and municipality population data from the US Census Bureau to assess the associations between state tobacco control policy variables and youth smoking outcomes, focusing on youths aged 12 to 17 years. We also examined the influence of policy variables on youth access when these variables were held at 2002 levels. Per capita funding for state tobacco control programs was negatively associated with all 4 smoking outcomes. Smoke-free air laws were negatively associated with all outcomes except past-year initiation, and cigarette prices were associated only with current smoking. We found no association between these outcomes and retailer compliance with youth access laws. Smoke-free air laws and state tobacco control programs are effective strategies for curbing youth smoking.


Enhancing knowledge discovery from cancer genomics data with Galaxy.
The field of cancer genomics has demonstrated the power of massively parallel sequencing techniques to inform on the genes and specific alterations that drive tumor onset and progression. Although large comprehensive sequence data sets continue to be made increasingly available, data analysis remains an ongoing challenge, particularly for laboratories lacking dedicated resources and bioinformatics expertise. To address this, we have produced a collection of Galaxy tools that represent many popular algorithms for detecting somatic genetic alterations from cancer genome and exome data. We developed new methods for parallelization of these tools within Galaxy to accelerate runtime and have demonstrated their usability and summarized their runtimes on multiple cloud service providers. Some tools represent extensions or refinement of existing toolkits to yield visualizations suited to cohort-wide cancer genomic analysis. For example, we present Oncocircos and Oncoprintplus, which generate data-rich summaries of exome-derived somatic mutation. Workflows that integrate these to achieve data integration and visualizations are demonstrated on a cohort of 96 diffuse large B-cell lymphomas and enabled the discovery of multiple candidate lymphoma-related genes. Our toolkit is available from our GitHub repository as Galaxy tool and dependency definitions and has been deployed using virtualization on multiple platforms including Docker.


Transmural activations and stimulus potentials in three-dimensional anisotropic canine myocardium.
Epicardial and endocardial pacing are widely used, yet little is known about the three-dimensional distribution of potentials generated by the pacing stimulus or the spread of activation from these pacing sites. In six open-chest dogs, simultaneous recordings were made from 120 transmural electrodes in 40 plunge electrodes within a 35 X 20 X 5-mm portion of the right ventricular outflow tract during epicardial and endocardial pacing at a strength of twice diastolic threshold and at 1 mA. The magnitude of extracellular potentials generated by the stimulus and the activation times were compared in regions proximal (less than 10-12 mm) and distal to the pacing site. Local fiber orientation was histologically determined at each recording electrode. For endocardial pacing, endocardial potentials were larger than epicardial potentials only in the proximal region (p less than 0.001); while in the distal region, epicardial potentials were larger (p less than 0.001), and endocardial activation occurred earlier than epicardial activation for both regions (p less than 0.001). For epicardial pacing, epicardial potentials were larger than endocardial potentials in both regions (p less than 0.001), and epicardial activation occurred earlier only in the proximal region (p less than 0.02), while endocardial activation occurred before epicardial activation in the distal region (p less than 0.01). In planes of recording electrodes parallel to the epicardium and endocardium, the initial isochrones were elliptical with the major axes of the ellipses along the mean fiber orientation between the pacing site and recording plane rather than along the local fiber orientation in the recording plane. Thus, the ellipses in each plane rotated with respect to each other so that in three dimensions the activation front was helicoid, yet the twist of the helix was less than that of the corresponding transmural rotation of fibers. For pacing from the right ventricular outflow tract, we conclude that beyond 10-12 mm from endocardial and epicardial pacing sites epicardial stimulus potentials in both cases are larger than endocardial potentials because of resistivity differences inside and outside the heart wall and activation in both cases is primarily endocardial to epicardial because of rapid endocardial conduction, and we conclude that the initial spread of activation is helicoid and determined by transmural fiber direction.


Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function.
Activated CD4 T cells proliferate rapidly and remodel epigenetically before exiting the cell cycle and engaging acquired effector functions. Metabolic reprogramming from the naive state is required throughout these phases of activation1. In CD4 T cells, T-cell-receptor ligation-along with co-stimulatory and cytokine signals-induces a glycolytic anabolic program that is required for biomass generation, rapid proliferation and effector function2. CD4 T cell differentiation (proliferation and epigenetic remodelling) and function are orchestrated coordinately by signal transduction and transcriptional remodelling. However, it remains unclear whether these processes are regulated independently of one another by cellular biochemical composition. Here we demonstrate that distinct modes of mitochondrial metabolism support differentiation and effector functions of mouse T helper 1 (TH1) cells by biochemically uncoupling these two processes. We find that the tricarboxylic acid cycle is required for the terminal effector function of TH1 cells through succinate dehydrogenase (complex II), but that the activity of succinate dehydrogenase suppresses TH1 cell proliferation and histone acetylation. By contrast, we show that complex I of the electron transport chain, the malate-aspartate shuttle and mitochondrial citrate export are required to maintain synthesis of aspartate, which is necessary for the proliferation of T helper cells. Furthermore, we find that mitochondrial citrate export and the malate-aspartate shuttle promote histone acetylation, and specifically regulate the expression of genes involved in T cell activation. Combining genetic, pharmacological and metabolomics approaches, we demonstrate that the differentiation and terminal effector functions of T helper cells are biochemically uncoupled. These findings support a model in which the malate-aspartate shuttle, mitochondrial citrate export and complex I supply the substrates needed for proliferation and epigenetic remodelling early during T cell activation, whereas complex II consumes the substrates of these pathways, which antagonizes differentiation and enforces terminal effector function. Our data suggest that transcriptional programming acts together with a parallel biochemical network to enforce cell state.


Overexpression of ß-Ketoacyl Co-A Synthase1 Gene Improves Tolerance of Drought Susceptible Groundnut (Arachis hypogaea L.) Cultivar K-6 by Increased Leaf Epicuticular Wax Accumulation.
Drought is one of the major environmental constraints affecting the crop productivity worldwide. One of the agricultural challenges today is to develop plants with minimized water utilization and reduced water loss in adverse environmental conditions. Epicuticular waxes play a major role in minimizing water loss. Epicuticular wax covers aerial plant parts and also prevents non-stomatal water loss by forming the outermost barrier from the surfaces. Epicuticular wax content (EWC) variation was found to be affiliated with drought tolerance of groundnut cultivars. In the current study, a fatty acid elongase gene, KCS1, which catalyzes a rate limiting step in the epicuticular wax biosynthesis was isolated from drought tolerant cultivar K-9 and overexpressed in drought sensitive groundnut cultivar (K-6) under the control of CaMV35S constitutive promoter. Transgenic groundnut plants overexpressing AhKCS1 exhibited normal growth and displaying greenish dark shiny appearance. Environmental scanning electron microscopy (ESEM) revealed the excess of epicuticular wax crystal depositions on the transgenic plant leaves compared to non-transgenic wild type plants. The findings were further supported by gas chromotography-mass spectroscopic analysis (GC-MS) that revealed enhanced levels of fatty acids, secondary alcohols, primary alcohols, aldehydes, alkanes, and ketones in transgenics compared to wild types. The AhKCS1 overexpressing transgenic groundnut plants exhibited increase in the cuticular wax content, reduction of water loss, lower membrane damage, decreased MDA content, and high proline content compared to that of non-transgenic groundnut plants. Our findings suggest that the AhKCS1 gene plays a major role in combating drought stress by preventing non-stomatal water loss in drought sensitive groundnut cultivar (K-6).


Effect of vitamin E source, natural versus synthetic, and quantity on serum and tissue alpha-tocopherol concentrations in finishing swine.
Relative vitamin E status of pigs fed natural or synthetic vitamin E was evaluated based on serum and tissue alpha-tocopherol concentrations. Individually fed finishing gilts at a BW of 70.5 kg (n = 24) were allotted to dietary treatments based on initial BW. The 5 dietary treatments consisted of a positive control diet using synthetic vitamin E acetate (Syn E Ac) supplemented at 22 mg/kg, and 4 dietary levels of natural vitamin E acetate (Nat E Ac) supplemented at 6.71, 8.33, 11.00, and 16.18 mg/kg of diet. Before initiation of the 32-d experiment, pigs were fed a non-vitamin E-fortified diet for 30 d. Diets were formulated to contain true ileal digestible lysine of 0.9 and 0.8% for the pretest and test diets. Serum samples were collected on d 15 and 32, whereas tissue samples were collected on d 32 for alpha-tocopherol analysis. Serum alpha-tocopherol concentrations on d 15 and 32 were greater (P < 0.05) in pigs fed 8.33, 11.00, or 16.18 mg/kg of Nat E Ac than in pigs fed 22 mg/kg of Syn E Ac. When compared with pigs fed 22 mg/kg of Syn E Ac, alpha-tocopherol concentrations were greater (P < 0.05) in 6 tissues (heart, kidney, spleen, liver, lung, and adipose) in pigs fed 16.18 mg/kg of Nat E Ac; greater (P < 0.05) in heart, kidney, spleen, liver, and adipose tissue in pigs fed 11.00 mg/kg of Nat E Ac; and greater (P < 0.05) in spleen, loin, and adipose tissue in pigs fed 8.33 mg/kg of Nat E Ac. As dietary Nat E Ac increased from 6.71 to 16.18 mg/kg, serum alpha-tocopherol increased linearly (P < 0.01) on d 15 and 32 of the experiment. Increasing dietary Nat E Ac linearly increased (P < 0.05) alpha-tocopherol concentrations for lung, heart, kidney, spleen, and liver. These results indicate that Nat E Ac was an effective vitamin E source and its relative bioavailability was substantially greater than 1.36 for finishing swine when compared with Syn E Ac.


Development of a Personalized m/eHealth Algorithm for the Resumption of Activities of Daily Life Including Work and Sport after Total and Unicompartmental Knee Arthroplasty: A Multidisciplinary Delphi Study.
Evidence for recommendations concerning the resumption of activities of daily life, including work and sport, after knee arthroplasty is lacking. Therefore, recommendations vary considerably between hospitals and healthcare professionals. We aimed to obtain multidisciplinary consensus for such recommendations. Using a Delphi procedure, we strived to reach consensus among a multidisciplinary expert panel of six orthopaedic surgeons, three physical therapists, five occupational physicians and one physician assistant on recommendations regarding the resumption of 27 activities of daily life. The Delphi procedure involved three online questionnaire rounds and one face-to-face consensus meeting. In each of these four rounds, experts independently decided at what time daily life activities could feasibly and safely be resumed after knee arthroplasty. We distinguished patients with a fast, average and slow recovery. After four Delphi rounds, the expert panel reached consensus for all 27 activities. For example, experts agreed that total knee arthroplasty patients with a fast recovery could resume cycling six weeks after the surgery, while those with an average and slow recovery could resume this activity after nine and twelve weeks, respectively. The consensus recommendations will subsequently be integrated into an algorithm of a personalized m/eHealth portal to enhance recovery among knee arthroplasty patients.


Joint thresholding and quantizer selection for transform image coding: entropy-constrained analysis and applications to baseline JPEG.
Striving to maximize baseline (Joint Photographers Expert Group-JPEG) image quality without compromising compatibility of current JPEG decoders, we develop an image-adaptive JPEG encoding algorithm that jointly optimizes quantizer selection, coefficient "thresholding", and Huffman coding within a rate-distortion (R-D) framework. Practically speaking, our algorithm unifies two previous approaches to image-adaptive JPEG encoding: R-D optimized quantizer selection and R-D optimal thresholding. Conceptually speaking, our algorithm is a logical consequence of entropy-constrained vector quantization (ECVQ) design principles in the severely constrained instance of JPEG-compatible encoding. We explore both viewpoints: the practical, to concretely derive our algorithm, and the conceptual, to justify the claim that our algorithm approaches the best performance that a JPEG encoder can achieve. This performance includes significant objective peak signal-to-noise ratio (PSNR) improvement over previous work and at high rates gives results comparable to state-of-the-art image coders. For example, coding the Lena image at 1.0 b/pixel, our JPEG encoder achieves a PSNR performance of 39.6 dB that slightly exceeds the quoted PSNR results of Shapiro's wavelet-based zero-tree coder. Using a visually based distortion metric, we can achieve noticeable subjective improvement as well. Furthermore, our algorithm may be applied to other systems that use run-length encoding, including intraframe MPEG and subband or wavelet coding.


Dimensions of homelessness.
Investigations of homelessness have been hampered by the lack of operational definitions sensitive enough to achieve subgroup differentiation and simple enough to permit replication. As a consequence, programming and policy development have often proceeded based on varying assessments of the composition, size, and needs of the homeless population. This paper describes the empirical use of duration of homelessness and dwelling place as elements of an operational definition of homelessness. The approach reflects a conceptualization of homelessness as a continuous variable that can be described by coordinates of time and place. A screening instrument that quantified the homeless experience was developed and evaluated in conjunction with a federally funded demonstration project for homeless substance-abusing men and women. Eight hundred and thirty-nine men and women from six public detoxification centers were screened over a two-year period that began in August 1988. Respondents were asked eight questions to assess duration (time) and location (place) of homelessness before they entered the detoxification center. A simple index was constructed retrospectively and found to differentiate the sample into homeless and near-homeless subgroups. Between-group differences were statistically significant in demographics, presenting problems, and probability for successful intervention. These data paralleled previously reported differences between homeless subgroups and support the concurrent validity of the index. Cronbach's alpha (.72) showed the index to be moderately reliable. Differentiation of homeless persons into meaningful subgroups appears possible and programmatically recommended. Homelessness is not a unitary phenomenon, and it is unlikely to respond to therapeutic interventions that fail to consider individual differences.


"Could I return to my life?" Integrated Narrative Nursing Model in Education (INNE).
The Integrated Narrative Nursing Model (INNM) is an approach that integrates the qualitative methodology typical of the human sciences, with the quantitative methodology more often associated with the natural sciences. This complex model, which combines a focus on narrative with quantitative measures, has recently been effectively applied to the assessment of chronic patients. In this study, the model is applied to the planning phase of education (Integrated Narrative Nursing Education, INNE), and proves to be a valid instrument for the promotion of the current educational paradigm that is centered on the engagement of both the patient and the caregiver in their own path of care. The aim of this study is therefore to describe the nurse's strategy in the planning of an educational intervention by using the INNE model. The case of a 70-year-old woman with pulmonary neoplasm is described at her first admission to Hospice. Each step conducted by the reference nurse, who uses INNE to record the nurse-patient narrative and collect subsequent questionnaires in order to create a shared educational plan, is also described. The information collected was submitted, starting from a grounded methodology to the following four levels of analysis: I. Needs Assessment, II. Narrative Diagnosis, III. Quantitative Outcome, IV. Integrated Outcome. Step IV, which is derived from the integration of all levels of analysis, allows a nurse to define, even graphically, the conceptual map of a patient's needs, resources and perspectives, in a completely tailored manner. The INNE model offers a valid methodological support for the professional who intends to educate the patient through an inter-subjective and engaged pathway, between the professional, their patient and the socio-relational context. It is a matter of adopting a complex vision that combines processes and methods that require a steady scientific basis and advanced methodological expertise with active listening and empathy - skills which require emotional intelligence.


A qualitative study of immigrant women on long-term sick leave and their experience of dignity.
The purpose of this study was to explore if and how immigrant women suffering from chronic pain experience and maintain their dignity, during rehabilitation. The study was designed as a field study, with participant observation and in-depth interviews. Participant observations were carried out during a rehabilitation course for 14 immigrant women on an outpatient clinic at a rehabilitation hospital in southern Norway. In-depth interviews were performed after the rehabilitation period. Hermeneutic analysis was applied to interpret the data. Findings show that the immigrant women experienced dignity by being seen, respected and believed by family-members, healthcare personnel and other patients at the outpatient clinic. Moreover, they maintained their dignity through a sense of their own value, integrity, religious faith and hope for the future. The immigrant women maintained and protected their dignity by finding strength, pride, and self-worth in their religion and through their family-members' affection. Taking responsibility for themselves and others and experiencing fellowship and equality with other women, they enhanced their dignity during their rehabilitation process. The caring attitudes and behavior of some healthcare personnel promoted patient dignity. They also gained hope and dignity by experiencing goodness, cultural competence, and sensitivity from healthcare personnel. Implications for rehabilitation This study shows that the family role is more important for the immigrant women than the role as an employee, although financial independence and being able to help relatives financially also were central. Fellowship and equality with other patients, together with a rehabilitation program, which is facilitated for different language levels, were understood as important factors for an effective recovery. Enough time to get to know the patients and cultural competence seems to be central components for the health care personnel to give efficient help to immigrants in rehabilitation. Immigrants from low/middle-income countries appear to apply their religiousness as a resource in their lives to a greater extent than native Norwegians do, and should be taken into consideration when planning and implementing rehabilitation programs for immigrants.


Identification of non-cross-linked compounds in methanolic extracts of cured and aged linseed oil-based paint films using gas chromatography-mass spectrometry.
Methanolic extracts of paint samples of different composition and age were qualitatively investigated by GC-MS using an on-column injector after off-line methylation or trimethylsilyl derivatisation, and on-line thermally assisted (trans)methylation with tetramethylammonium hydroxide using Curie-point pyrolysis-GC-MS. The combination of these three analytical strategies led to the identification of typical oxidation products of unsaturated fatty acids by interpretation of their mass spectrum. Some of the identified compounds have not been reported before. Both the off-line and on-line GC-MS strategy show series of short-chain fatty (di)acids and C16 and (oxidised) C18 fatty acids. The major advantage of the on-line pyrolysis-GC-MS approach is that chemical work-up is minimal and very quick. With this technique both the carboxylic acid functionalities, and hydroxyl groups are methylated. Young paint films are shown to contain relatively more oxidised C18 fatty acids and less diacids compared to older paints, which is indicative for the on-going oxidation processes within the paint. After trimethylsilylation, monoacylglycerols are detected indicative for hydrolytic processes, which reflect the relative distribution of the most prominent silylated fatty acids present. Relatively more C16 and C18 monoacylglycerols are found in young paints, whereas older paints contain higher amounts of monoacylglycerols of diacids.


LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation.
Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking - an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness.


Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.
In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 mumol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 mumol/L nitrendipine or 10 mumol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na(+)-Ca2+ exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na(+)-Ca2+ exchange. Because we could not directly assess the role of Na(+)-Ca2+ exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator veratridine or the sodium ionophore monensin. Superfusion with 1 mumol/L veratridine increased atrial natriuretic peptide secretion by 2.3-fold, and 1, 5, and 10 mumol/L monensin increased secretion by 1.1-, 2.1-, and 15.7-fold, respectively. In addition, we examined the possibility that the reported rise in intracellular sodium associated with increased beat frequency was due to enhanced Na(+)-H+ antiporter activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS) stem/progenitor cell activity regardless of ErbB2 status.
Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal) and SUM225 (ErbB2-overexpressing) and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.


Normal tissue radioprotection by amifostine via Warburg-type effects.
The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer.


Transmural cardiac strains in the lateral wall of the ovine left ventricle.
The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.


Epitope location in the Cryptococcus neoformans capsule is a determinant of antibody efficacy.
Monoclonal antibodies (mAbs) to the polysaccharide capsule of Cryptococcus neoformans can prolong survival in mice. However, the properties of antibodies that mediate protection are not fully understood. The IgM mAbs 12A1 and 13F1 originated from the same B cell and differ only by somatic mutations in their variable regions; yet mAb 12A1 protects against serotype D infection, while mAb 13F1 does not. Phage peptide display libraries were used to analyze the fine specificity of these two mAbs. The selection of distinct peptide motifs from identical libraries confirmed that mAbs 12A1 and 13F1 bound to two distinct epitopes. Immunofluorescence and immunoelectron microscopy studies revealed differences in antibody localization within the capsule of serotype D strain; mAb 12A1 bound to the outer rim of the capsule resulting in an annular pattern, whereas mAb 13F1 bound throughout the capsule and had a punctate appearance. The difference in the binding pattern of mAb 12A1 and 13F1 was not observed on serotype A organisms, where both mAbs bound to the capsule with an annular fluorescence pattern. The fluorescence pattern of binding correlated with protective efficacy; mAb 13F1 prolonged survival of mice infected with the J11 serotype A strain (annular fluorescence), but not serotype D strains (punctate pattern). Annular binding, but not punctate binding, was associated with increased opsonic efficacy for phagocytosis of C. neoformans by J774.16 macrophage-like cells. The correlation between capsular binding pattern, opsonic activity, and ability to prolong survival suggests that the efficacy of anticryptococcal antibodies is dependent upon where they bind in the polysaccharide capsule.


Candidatus Desulfofervidus auxilii, a hydrogenotrophic sulfate-reducing bacterium involved in the thermophilic anaerobic oxidation of methane.
The anaerobic oxidation of methane (AOM) is mediated by consortia of anaerobic methane-oxidizing archaea (ANME) and their specific partner bacteria. In thermophilic AOM consortia enriched from Guaymas Basin, members of the ANME-1 clade are associated with bacteria of the HotSeep-1 cluster, which likely perform direct electron exchange via nanowires. The partner bacterium was enriched with hydrogen as sole electron donor and sulfate as electron acceptor. Based on phylogenetic, genomic and metabolic characteristics we propose to name this chemolithoautotrophic sulfate reducer Candidatus Desulfofervidus auxilii. Ca. D. auxilii grows on hydrogen at temperatures between 50°C and 70°C with an activity optimum at 60°C and doubling time of 4-6 days. Its genome draft encodes for canonical sulfate reduction, periplasmic and soluble hydrogenases and autotrophic carbon fixation via the reductive tricarboxylic acid cycle. The presence of genes for pili formation and cytochromes, and their similarity to genes of Geobacter spp., indicate a potential for syntrophic growth via direct interspecies electron transfer when the organism grows in consortia with ANME. This first ANME-free enrichment of an AOM partner bacterium and its characterization opens the perspective for a deeper understanding of syntrophy in anaerobic methane oxidation.


Phenotypic expression of recombinant plasmids pKT107 and pHK11 in an avirulent avian Escherichia coli.
An avirulent wild-type avian Escherichia coli strain (Av) was electrotransformed with plasmids coding for complement resistance (pKT107) and Colicin V (ColV) production (pHK11) in order to study the effects of complement resistance and ColV production on virulence. Transformants were also compared with the wild type for embryo lethality, uptake by macrophages, motility, growth rate, plasmid content, and hemolysis. Growth rates and complement resistance patterns of strain Av and transformant Av+pHK11 were similar, but Av+pHK11 caused a significantly greater number of deaths in embryos and acquired motility. Transformant Av+pKT107 had a lower rate of phagocytosis, a slower growth rate, and a greater sensitivity to complement, and it changed from being non-hemolytic to expressing alpha-hemolytic action. The 35-kb plasmid present in the wild type was not present in the transformants. Although some of the results demonstrate the difficulties encountered in using wild-type organisms as recipients in virulence studies, the results with Av+pHK11 indicate that ColV production plus the acquisition of motility contributes to the virulence of avian E. coli.


A herpes simplex virus mutant in which glycoprotein D sequences are replaced by beta-galactosidase sequences binds to but is unable to penetrate into cells.
Herpes simplex virus (HSV) glycoprotein gD is a major component of the virion envelope and is thought to play an important role in the initial stages of viral infection and stimulates the production of high titers of neutralizing antibodies. We assumed that gD plays an essential role in virus replication, and so to complement viruses with mutations in the gD gene we constructed a cell line, denoted VD60, which is capable of expressing high levels of gD after infection with HSV. A recombinant virus, designated F-gD beta, in which sequences encoding gD and a nonessential glycoprotein, gI, were replaced by Escherichia coli beta-galactosidase sequences, was selected on the basis that it produced blue plaques on VD60 cell monolayers under agarose overlays containing 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). F-gD beta was able to replicate normally on complementing VD60 cells. However, F-gD beta was unable to form plaques on noncomplementing Vero cells. Virions lacking gD were produced in normal amounts by Vero cells infected with F-gD beta, and the virus particles were distributed throughout the cytoplasm and on the cell surface, suggesting that gD is not essential for HSV envelopment and egress. Virions lacking gD were able to bind to cells, but were unable to initiate synthesis of viral early polypeptides. Plaque production of F-gD beta particles lacking gD was enhanced by polyethylene glycol treatment, suggesting that gD is essential for penetration of HSV into cells. Other HSV glycoproteins have been implicated in the entry of virus into cells, and thus this process appears to involve multiple interactions at the cell surface.


Assessment of experts' approach to insulin therapy and development of a simulator for diabetes insulin adjustment.
To develop a computer program (Macintosh) to predict changes in blood glucose after changes in insulin dose, timing, and regimen. We established program parameters (apparent insulin action profiles; different for insulin-dependent and non-insulin-dependent diabetes mellitus) to match predictions by five diabetes specialists at our hospital of blood glucose changes after insulin-dose adjustment in 22 hypothetical patient cases. We compared the action profiles, which represent the blood glucose changes predicted by the experts with glucose-clamp studies of insulin action. We tested the program's performance in 22 different hypothetical cases against the responses of 15 specialists from outside our hospital. The specialists, when predicting effects of insulin dose adjustment, integrate numerous processes (insulin action, diet, sequential blood glucose interactions). They could not specify algorithms for determining these individual factors, but they could easily predict the overall effect in the context of patient cases. The computer program's insulin-action profiles simulate this "composite" approach. The developed program incorporates multiple insulin regimens, which may be changed during the stimulation, and adjusts predicted responses according to the patient's estimated sensitivity to insulin. Its predicted change in 172 blood glucose levels (22 cases) correlated well with the corresponding means of the outside specialists (r = 0.83, P = 0.0001). Comparing this correlation with that of individual specialists ranked the program third. A computer program can simulate specialists' "composite" approach (not based purely on conscious application of physiological data) to insulin adjustment.


Using correlational evidence to select youth for prevention programming.
In a period of increased accountability and reduced prevention resources, the effective targeting of those limited resources is critical. One way in which limited resources are focused is to identify and provide services to those most at risk for later substance use. Risk status, or propensity, is typically estimated from correlational evidence. Using meta-analytic techniques this paper examines the evidence that 29 of the 35 constructs specified by the CTC risk and protective factor model are related to alcohol, tobacco, or marijuana use. While these factors are generally demonstrated to be predictive of substance use, the strength of relation is modest. Ten factors show a significantly different strength of relation with tobacco than with alcohol and marijuana. Given the correlations observed and the rate of substance use in the population, providing only selective intervention services likely ignores the majority of those who will later use substances. Although selection improves the percentage of those receiving services who are likely to benefit from services, the evidence summarized in this study suggests selective interventions will omit many of those who will likely use substances. Given typical base and selection rates, smaller program effects on universal populations may keep a greater number of youth from becoming alcohol, tobacco, or marijuana involved. EDITORS' STRATEGIC IMPLICATIONS: The data make a strong and provocative argument for primary prevention of youth substance abuse that should be heard by policymakers and service providers involved in strategic planning and appropriate deployment of resources.


Effect of COVID-19 vaccine allocation strategies on vaccination refusal: A national survey.
Currently, one of the most pressing public health challenges is encouraging people to get vaccinated against COVID-19. Due to limited supplies, some people have had to wait for the COVID-19 vaccine. Consumer research has suggested that people who are overlooked in initial distribution of desired goods may no longer be interested. Here, we therefore examined people's preferences for proposed vaccine allocation strategies, as well as their anticipated responses to being overlooked. After health-care workers, most participants preferred prioritizing vaccines for high-risk individuals living in group-settings (49%) or with families (29%). We also found evidence of reluctance if passed over. After random assignment to vaccine allocation strategies that would initially overlook them, 37% of participants indicated that they would refuse the vaccine. The refusal rate rose to 42% when the vaccine allocation strategy prioritized people in areas with more COVID-19 - policies that were implemented in many areas. Even among participants who did not self-identify as vaccine hesitant, 22% said they would not want to vaccine in that case. Logistic regressions confirmed that vaccine refusal would be largest if vaccine allocation strategies targeted people who live in areas with more COVID-19 infections. In sum, once people are overlooked by vaccine allocation, they may no longer want to get vaccinated, even if they were not originally vaccine hesitant. Vaccine allocation strategies that prioritize high-infection areas and high-risk individuals in group-settings may enhance these concerns.


Magnetic resonance imaging detection of prostate cancer in men with previous negative prostate biopsy.
Use of transrectal ultrasound guided systematic prostate biopsy has poor diagnostic accuracy for prostate cancer (PCa) detection. Recently multiparametric MRI (mpMRI) of the prostate and MR/US fusion biopsy has been gaining popularity for men who have previously undergone a negative biopsy. We performed PubMed® and Web of Science® searches to identify studies on this subject, particularly focusing on studies consisting of patients who have had at least one previously negative biopsy. Across the literature, when a suspicious lesion is found on mpMRI, MR/US fusion biopsy has consistently demonstrated higher detection rate for any PCa and clinically significant PCa (csPCa) compared to the traditional repeat systematic biopsy (SB) approach. Furthermore, anteriorly located tumors are frequently identified using MR targeted biopsy (TB), suggesting that an MR guided approach allows for increased accuracy for detecting tumors commonly missed by systematic biopsies. We conclude that men with a prior negative biopsy and continued suspicion of PCa should strongly be encouraged to get a prostate mpMRI prior to a repeat biopsy.


Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex.
Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action-related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying semantic information.


TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.
While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8⁺ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8⁺ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8⁺ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy.


An unusual case of foreign body aspiration mimicking cavitary tuberculosis in adolescent patient: thread aspiration.
Foreign body aspiration continues to be a serious problem in childhood and adolescent period with significant rate of morbidity and rarely mortality. Half of the foreign body aspiration cases have no history of aspiration. The main foreign bodies inhaled are food fragments and different kinds of metallic objects. A 12-year-old girl was referred to the pediatric pulmonology department for chronic cough and hemoptysis. She had persistent infiltration and cavitary lesion mimicking cavitary tuberculosis. There was no contact history with tuberculosis in her family and acid resistant bacillus was not found in the sputum examination. Flexible bronchoscopy was performed for persistent infiltration and hemoptysis and inflamed thread was found in right lower lobe bronchus. This is the first case of thread inhalation mimicking cavitary tuberculosis in an adolescent patient.


Parallel evolution in Ugandan crater lakes: repeated evolution of limnetic body shapes in haplochromine cichlid fish.
The enormous diversity found in East African cichlid fishes in terms of morphology, coloration, and behavior have made them a model for the study of speciation and adaptive evolution. In particular, haplochromine cichlids, by far the most species-rich lineage of cichlids, are a well-known textbook example for parallel evolution. Southwestern Uganda is an area of high tectonic activity, and is home to numerous crater lakes. Many Ugandan crater lakes were colonized, apparently independently, by a single lineage of haplochromine cichlids. Thereby, this system could be considered a natural experiment in which one can study the interaction between geographical isolation and natural selection promoting phenotypic diversification. We sampled 13 crater lakes and six potentially-ancestral older lakes and, using both mitochondrial and microsatellite markers, discovered strong genetic and morphological differentiation whereby (a) geographically close lakes tend to be genetically more similar and (b) three different geographic areas seem to have been colonized by three independent waves of colonization from the same source population. Using a geometric morphometric approach, we found that body shape elongation (i.e. a limnetic morphology) evolved repeatedly from the ancestral deeper-bodied benthic morphology in the clear and deep crater lake habitats. A pattern of strong genetic and morphological differentiation was observed in the Ugandan crater lakes. Our data suggest that body shape changes have repeatedly evolved into a more limnetic-like form in several Ugandan crater lakes after independent waves of colonization from the same source population. The observed morphological changes in crater lake cichlids are likely to result from a common selective regime.


Differential requirements in endocytic trafficking for penetration of dengue virus.
The entry of DENV into the host cell appears to be a very complex process which has been started to be studied in detail. In this report, the route of functional intracellular trafficking after endocytic uptake of dengue virus serotype 1 (DENV-1) strain HW, DENV-2 strain NGC and DENV-2 strain 16681 into Vero cells was studied by using a susceptibility to ammonium chloride assay, dominant negative mutants of several members of the family of cellular Rab GTPases that participate in regulation of transport through endosome vesicles and immunofluorescence colocalization. Together, the results presented demonstrate that in spite of the different internalization route among viral serotypes in Vero cells and regardless of the viral strain, DENV particles are first transported to early endosomes in a Rab5-dependent manner. Then a Rab7-dependent pathway guides DENV-2 16681 to late endosomes, whereas a yet unknown sorting event controls the transport of DENV-2 NGC, and most probably DENV-1 HW, to the perinuclear recycling compartments where fusion membrane would take place releasing nucleocapsid into the cytoplasm. Besides the demonstration of a different intracellular trafficking for two DENV-2 strains that shared the initial clathrin-independent internalization route, these studies proved for the first time the involvement of the slow recycling pathway for DENV-2 productive infection.


Driving with navigational instructions: Investigating user behaviour and performance.
This paper reports the results of an inter-disciplinary study investigating user preferences and performance in relation to spoken in-car route guidance. In-car navigation systems are becoming increasingly popular. However, despite large amounts of research assessing the presentation of spatial information, and the usability and interaction issues surrounding the interfaces, there has been much less investigation of the impacts of auditory presentation of route information. We addressed this issue using a multi-disciplinary approach to collect both qualitative and quantitative data through questionnaires and user experiments. Our research identified a user preference for auditory presentation of route information, as well as a memory advantage for auditory over visual presentation. We also found that simple auditory route instructions could be followed without significant interference to a simulated driving task, whereas more complex auditory instructions did cause interference. Taken together, this research highlights the importance of the design of spoken route guidance instructions in minimising the cognitive demands that they impose.


Response to 'comment on recent modeling studies of astrocyte-neuron metabolic interactions': much ado about nothing.
For many years, a tenet of cerebral metabolism held that glucose was the obligate energy substrate of the mammalian brain and that neuronal oxidative metabolism represented the majority of this glucose utilization. In 1994, Pellerin and Magistretti formulated the astrocyte-neuron lactate shuttle (ANLS) hypothesis, in which astrocytes, not neurons, metabolized glucose, with subsequent transport of the glycolytically derived lactate to fuel the energy needs of the neuron during neurotransmission. By considering the concentrations and kinetic characteristics of the nutrient transporter proteins, Simpson et al later supported the opposite view, in which lactate flows from neurons to astrocytes, thus leading to the neuron-astrocyte lactate shuttle (NALS). Most recently, a commentary was published in this journal attempting to discredit the NALS. This challenge has stimulated the present response in which we detail the inaccuracies of the commentary and further model several different possibilities. Although our simulations continue to support the predominance of neuronal glucose utilization during activation and neuronal to astrocytic lactate flow, the most important result is that, regardless of the direction of the flow, the overall contribution of lactate to cerebral glucose metabolism is found to be so small as to make this ongoing debate 'much ado about nothing'.


Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection.
In patients with HIV encephalitis, activated macrophages and microglial cells in the brain are infected by the human immunodeficiency virus (HIV-1). Immune activation can release neurotoxic chemicals including cytokines, free radicals, autocoids, and hydrolytic enzymes. In this study, the presence of hydrolytic enzymes in acquired immune deficiency syndrome (AIDS)-related neurodegeneration was addressed. Activities of four lysosomal hydrolases were assayed in the frontal lobe of 69 males who died with AIDS and 31 age-matched control men. Activities of all four enzymes were increased significantly (1.6 to 3.6 times) in white matter of patients with AIDS. Less pronounced increases were present in cerebral cortex. Of 69 of the subjects with AIDS, 50 (72%), had at least one abnormally active enzyme. Patients with HIV encephalitis and other neuropathological changes were affected as were many subjects without any clear neuropathological anomaly. Lysosomal cathepsin D immunostaining revealed increased lysosomes within perivascular macrophages, multinucleated cells, activated microglial cells, and hypertrophic astrocytes. Increased enzyme activity was correlated significantly with assay results for HIV-1 DNA using the polymerase chain reaction. The release of acid hydrolases associated with cerebral HIV-1 infection could lead to unopposed hydrolysis of matrix and surface proteins. These post-translational disturbances could contribute to white matter and synaptic injury in AIDS.


Implementation science: promoting science-based approaches to prevent teen pregnancy.
This paper reports the results of a project funded by the Centers for Disease Control and Prevention intended to promote the use of science-based approaches to teen pregnancy prevention. As with other efforts to promote diffusion of innovations, adoption of these successful programs faced a number of barriers including lack of knowledge of programs that work, lack of funding for training and materials, devaluing science-based approaches, complexity of successful programs, politics, funding streams and compatibility with particular community characteristics. Nevertheless, five state and three national teen pregnancy organizations provided intensive technical assistance, produced materials, and provided training to encourage use of programs that work. Local barriers to their work included the fact that teen pregnancy rates were already dropping, instability of funding to pay for such programs, turnover of agency staff, the need for intensive follow-up to promote adoption, the internal organization of the initiative, and the fragility of local teen pregnancy prevention coalitions. Still, in each of five states, there was increased adoption of science-based approaches to prevent teen pregnancy.


Development and Validation of the Treatment Attrition-Retention Scale for Personality Disorders.
This study is an investigation of the psychometric properties of the Treatment Attrition-Retention Scale for Personality Disorders (TARS-PD), an instrument developed to identify patients with personality disorder (PD) at risk of early dropout from psychotherapy. In a first study, assessment files from 320 patients referred for PD evaluation at an outpatient clinic were examined to assess the instrument's inter-rater reliability, construct validity, and discriminant validity. Results showed that the global scale could be scored with excellent reliability. Exploratory factor analysis identified five factors: Narcissism, Psychopathy, Secondary gains, Low motivation, and Cluster A features. A second study focused on the scale's predictive validity. The TARS-PD showed high specificity (94%) in identifying dropouts, using a cut-off of ≥ 10. Both global and factor scores from the TARS-PD were significant predictors of treatment status (dropout vs. continuation) at 6 months. The scale should be considered promising for PD evaluation and treatment planning.


Residual Femoral Deformity and Femoroacetabular Impingement after Intertrochanteric Osteotomy for Slipped Capital Femoral Epiphysis.
We retrospectively reviewed 29 hips in which intertrochanteric osteotomies were performed for severe slipped capital femoral epiphyses. Mean age at surgery: 12.6 years. Mean follow-up period: 6 years. At the final follow-up evaluation, one patient had coxalgia, and six hips showed a limited range of motion. A pistol-grip deformity was observed in 13 hips, osteoarthritis in two hips, and a bump existed in 19 hips on the latest radiographs. Gradual remodeling of the bumps was observed post-operatively in 22 hips. The mean α and β angles and offset α and β improved over time. The remodeling proceeded rapidly for 1 year post-surgery. We compared hips classified as β angles of ≥ 63° to < 63° at the final follow-up evaluation, the mean β angle 1 year post-surgery, and the mean ratio of improvement of the β angle per year from 1 year post-surgery to the final follow up, which differed significantly. Nearly all of the patients who underwent intertrochanteric osteotomies had residual morphologic abnormalities, but few had clinical symptoms. The β angle 1 year post-surgery and the ratio of remodeling of the bump from 1 year post-surgery to the final follow-up can be regarded as a potential predictor of morphologic results after intertrochanteric osteotomy.


Towards equitable conservation: Social capital, fear and livestock loss shape perceived benefit from a protected area.
Providing sufficient benefits to local people can be an important component of effective and equitable conservation, especially where local communities face substantial opportunity costs or disbenefits from conservation. However, the distribution of benefits to local people is often inadequate or inequitable. In this study we investigated the heterogeneity in the extent to which people living near Hwange National Park (HNP), Zimbabwe, perceive benefit from the presence of the park. Specifically, we examined the relationships between a diverse set of candidate predictor variables and perceived benefit from HNP. Our candidate predictor variables broadly relate to personal assets, social capital, value orientation, fear of lions, and belief and participation in human-wildlife conflict mitigation schemes. One third of respondents reported that their household experienced at least some benefits from HNP. Of all respondents, 6% perceived their household to benefit strongly from HNP and 2% very strongly. Livestock loss to wildlife was the most important factor for predicting perceived benefit, with those suffering more loss less likely to perceive benefit. Multiple demographic factors predicted perceived benefit with, for instance, older people and those with less education perceiving less benefit. Employment in conservation-related work positively affected perceived benefit, whereas fear of lions had a negative impact. Social capital appeared to have a positive influence on perceived benefit from HNP. The relationship between social capital and perceived benefit was positive and plateauing, which suggests that social capital is especially impactful on the benefit perceived by individuals reporting the least social capital. We also found a positive association between belief in compensation schemes and perceived benefit from HNP. We posit hypotheses for this association but are unable to determine the underlying drivers of this relationship. Finally, participation in the community guardians programme, a human-lion conflict mitigation programme, was positively related to perceived benefit from HNP. Thus, our findings emphasise the value of considering a diverse array of factors when investigating park-people relationships and yield insights for improving the equitability of conservation in and around HNP and similar systems.


Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population.
Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population. The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale - Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5'-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R. Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function. We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.