Intensive skills week for military medical students increases technical proficiency, confidence, and skills to minimize negative stress.
The effects of stress induced cortisol on learning and memory is well documented in the literature.1-3 Memory and learning are enhanced at low levels while high levels are detrimental. Repetitive training in stressful situations enables management of the stress response4 as demonstrated by the high intensity training military members undergo to prepare for tactical situations. Appropriate management of one?s stress response is critical in the medical field, as the negative effects of stress can potentially hinder life-saving procedures and treatments. This also applies to physicians-in-training as they learn and practice triage, emergency medicine, and surgical skills prior to graduation. Rocky Vista University?s Military Medicine Honor?s Track (MMHT) held a week long high-intensity emergency medicine and surgical Intensive Skills Week (ISW), facilitated by military and university physicians, to advance students? skills and maximize training using the Human Worn Partial Surgical Task Simulator (Cut Suit). The short-term goal of the ISW was to overcome negative stress responses to increase confidence, technical and non-technical knowledge, and skill in surgery and emergency medicine in an effort to improve performance as third-year medical students. The long-term goal was to enhance performance and proficiency in residency and future medical practice. The metrics for the short-term goals were the focus of this pilot study. Results show an increase in confidence and decrease in perceived stress as well as statistically significant improvements in technical and non-technical skills and surgical instrumentation knowledge throughout the week. There is a correlative benefit to physician and non-physician military personnel, especially Special Operations Forces (SOF) medical personnel, from developing and implementing similar training programs when live tissue or cadaver models are unavailable or unfeasible.


Linear single-step image reconstruction in the presence of nonscattering regions.
There is growing interest in the use of near-infrared spectroscopy for the noninvasive determination of the oxygenation level within biological tissue. Stemming from this application, there has been further research in using this technique for obtaining tomographic images of the neonatal head, with the view of determining the level of oxygenated and deoxygenated blood within the brain. Because of computational complexity, methods used for numerical modeling of photon transfer within tissue have usually been limited to the diffusion approximation of the Boltzmann transport equation. The diffusion approximation, however, is not valid in regions of low scatter, such as the cerebrospinal fluid. Methods have been proposed for dealing with nonscattering regions within diffusing materials through the use of a radiosity-diffusion model. Currently, this new model assumes prior knowledge of the void region; therefore it is instructive to examine the errors introduced in applying a simple diffusion-based reconstruction scheme in cases where a nonscattering region exists. We present reconstructed images, using linear algorithms, of models that contain a nonscattering region within a diffusing material. The forward data are calculated by using the radiosity-diffusion model, and the inverse problem is solved by using either the radiosity-diffusion model or the diffusion-only model. When using data from a model containing a clear layer and reconstructing with the correct model, one can reconstruct the anomaly, but the qualitative accuracy and the position of the reconstructed anomaly depend on the size and the position of the clear regions. If the inverse model has no information about the clear regions (i.e., it is a purely diffusing model), an anomaly can be reconstructed, but the resulting image has very poor qualitative accuracy and poor localization of the anomaly. The errors in quantitative and localization accuracies depend on the size and location of the clear regions.


Self-change: A pathway to cannabis abuse resolution.
Long-term daily cannabis abusers (N = 25) who without treatment stopped using cannabis for at least one year were interviewed about their past substance use, antecedents to change, and factors supportive of change. Respondents' cannabis problems decreased in the year prior to their recovery compared to their lifetime use. Respondents described their successful quit attempts through structured interviews and autobiographical narratives. The narratives were content analyzed for factors related to recovery. The reports indicated that marijuana cessation was motivated more by internal than external factors, and the most common precipitants of quit attempts were cognitive anti-cannabis factors. The major reason reported by respondents for stopping cannabis was a change in how they viewed their cannabis use, followed by negative personal effects. The most common reported maintenance factors were avoidance of situations in which cannabis was used, changes in lifestyle, and the development of non-cannabis-related interests. Cognitive and respiratory functioning were also assessed. Lastly, more than 75% of respondents reported not seeking treatment because they believed it was not needed or because they wanted to quit on their own. Directions for future research are offered.


Food and nutrient intake, anthropometric measurements and smoking according to alcohol consumption in the EPIC Heidelberg study.
The study was carried out to determine associations of reported alcohol intake with dietary habits, body mass index, waist-to-hip ratio (WHR) and smoking. 24,894 subjects who participated in the baseline examination of the German part of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg and were between 35 and 65 years of age at baseline were included in the present cross-sectional analysis (11,617 men, 13,277 women). Diet and alcohol consumption were assessed with a semiquantitative food frequency questionnaire. Analysis of covariance with age as a covariate was used to analyse the association between alcohol intake and dietary consumption patterns, BMI, WHR and smoking. Alcohol did not replace other food items, but was an addition to the diet. Among alcohol consumers, fat and protein intake as a percentage of energy was slightly higher and carbohydrate intake was slightly lower than among abstainers. Alcohol consumers had a lower intake of fruits, dairy products, cereal products, and added vegetable fat and a higher intake of animal products such as meat, fish, eggs and added animal fat than abstainers. The prevalence of current smoking showed a U-shaped relation to alcohol intake in men and women. In men, a U-shaped association was also seen between the prevalence of former smoking and alcohol intake, while the prevalence of former smoking increased linearly with alcohol intake in women. The results show that alcohol consumption is associated with dietary consumption patterns and smoking. Therefore, it will be important to consider dietary patterns and other lifestyle parameters when investigating the health effects of alcohol intake in the future.


Effectiveness of sensor monitoring in an occupational therapy rehabilitation program for older individuals after hip fracture, the SO-HIP trial: study protocol of a three-arm stepped wedge cluster randomized trial.
The performance of activities of daily living (ADL) at home is important for the recovery of older individuals after hip fracture. However, 20-90% of these individuals lose ADL function and never fully recover. It is currently unknown to what extent occupational therapy (OT) with coaching based on cognitive behavioral treatment (CBT) improves recovery. The same holds for sensor monitoring-based coaching in addition to OT. Here, we describe the design of a study investigating the effect of sensor monitoring embedded in an OT rehabilitation program on the recovery of ADL among older individuals after hip fracture. Six nursing homes will be randomized in a three-arm stepped wedge cluster randomized trial. All nursing homes will initially provide standard care. At designated time points, nursing homes, successively and in random order, will cross over to the provision of OT and at the next time point, to sensor monitoring-enhanced OT. A total of 288 older individuals, previously living alone in the community, who after a hip fracture were admitted to a geriatric rehabilitation ward for a short-term rehabilitation, will be enrolled. Individuals in the first intervention group (OTc) will participate in an OT rehabilitation program with coaching based on cognitive behavioral therapy (CBT) principles. In the sensor monitoring group, sensor monitoring is added to the OT intervention (OTcsm). Participants will receive a sensor monitoring system consisting of (i) an activity monitor during nursing home stay, (ii) a sensor monitoring system at home and a (iii) a web-based feedback application. These components will be embedded in the OT. The OT consists of a weekly session with an occupational therapist during the nursing home stay followed by four home visits and four telephone consultations. The primary outcome is patient-perceived daily functioning at 6 months, assessed using the Canadian Occupational Performance Measure (COPM). As far as we know, this study is the first large-scale stepped wedge trial, studying the effect of sensor monitoring embedded in an OT coaching program. The study will provide new knowledge on the combined intervention of sensor monitoring and coaching in OT as a part of a rehabilitation program to enable older individuals to perform everyday activities and to remain living independently after hip fracture. Netherlands National Trial Register, NTR 5716 Date registered: April 1 2016.


Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of Intestinal Diseases) Study.
Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.


A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E.
Soluble suppressor factor (SSF), first described in association with HIV-1 infection in vivo, is a molecule(s) capable of inhibiting T cell-dependent immune reactivity. Its relationship to human immunodeficiency virus (HIV) was further defined as supernatants of mononuclear cell cultures from HIV-1-seropositive carriers, CD4+ T lymphocytes infected with HIV-1 in vitro, and a T cell hybridoma incorporating CD4+ lymphocytes from an HIV-1-seropositive individual were shown to elaborate factors with similar activity profiles. These factors were recognized antigenically by certain antibodies directed against epitopes of p15E, a transmembrane protein of murine leukemia virus which shares regions of identity with proteins deduced from human endogenous retroviral envelope transcripts as well as HIV. These reagents precipitated a single-chain, nonglycosylated, nonviral protein of molecular weight 57,000 Da from SSF-producing cells. There was no cross-reactivity with antisera recognizing the IL-2R alpha-chain (CD25) or tumor necrosis factor. This molecule was present in very low levels in PHA-activated T lymphocytes and was upregulated following their infection with HIV-1. Isolation of HIV-linked SSF should permit comparisons with other virion, cellular, and serum inhibitory substances described in AIDS, and perhaps suggest therapeutic strategies.


Fortifying the forest: thinning and burning increase resistance to a bark beetle outbreak and promote forest resilience.
Fire frequency in low-elevation coniferous forests in western North America has greatly declined since the late 1800s. In many areas, this has increased tree density and the proportion of shade-tolerant species, reduced resource availability, and increased forest susceptibility to forest insect pests and high-severity wildfire. In response, treatments are often implemented with the goal of increasing ecosystem resilience by increasing resistance to disturbance. We capitalized on an existing replicated study of fire and stand density treatments in a ponderosa pine (Pinus ponderosa)-Douglas-fir (Pseudotsuga menziesii) forest in western Montana, USA, that experienced a naturally occurring mountain pine beetle (MPB; Dendroctonus ponderosae) outbreak 5 yr after implementation of fuels treatments. We explored whether treatment effects on tree-level defense and stand structure affected resistance to MPB. Mortality from MPB was highest in the denser, untreated control and burn-only treatments, with approximately 50% and 39%, respectively, of ponderosa pine killed during the outbreak, compared to almost no mortality in the thin-only and thin-burn treatments. Thinning treatments, with or without fire, dramatically increased tree growth and resin ducts relative to control and burn-only treatments. Prescribed burning did not increase resin ducts but did cause changes in resin chemistry that may have affected MPB communication and lowered attack success. While ponderosa pine remained dominant in the thin and thin-burn treatments after the outbreak, the high pine mortality in the control and burn-only treatment caused a shift in species dominance to Douglas-fir. The high Douglas-fir component in the control and burn-only treatments due to 20th century fire exclusion, coupled with high pine mortality from MPB, has likely reduced resilience of this forest beyond the ability to return to a ponderosa pine-dominated system in the absence of further fire or mechanical treatment. Our results show treatments designed to increase resistance to high-severity fire in ponderosa pine-dominated forests in the Northern Rockies can also increase resistance to MPB, even during an outbreak. This study suggests that fuel and restoration treatments in fire-dependent ponderosa pine forests that reduce tree density increase ecosystem resilience in the short term, while the reintroduction of fire is important for long-term resilience.


Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology.
In 2008, the U.S. Food and Drug Administration (FDA) issued an alert to health care professionals about an increased risk of suicide ideation and suicide behavior in people treated with antiepileptic drugs (AEDs). Since then, a number of retrospective cohort and case-control studies have been published that are trying to address this issue, but gathered results are contradictory. This report represents an expert consensus statement developed by an ad hoc task force of the Commission on Neuropsychobiology of the International League Against Epilepsy (ILAE). Although some (but not all) AEDs can be associated with treatment-emergent psychiatric problems that can lead to suicidal ideation and behavior, the actual suicidal risk is yet to be established, but it seems to be very low. The risk of stopping AEDs or refusing to start AEDs is significantly worse and can actually result in serious harm including death to the patient. Suicidality in epilepsy is multifactorial, and different variables are operant. Clinicians should investigate the existence of such risk factors and adopt appropriate screening instruments. If necessary, patients should be referred for a psychiatric evaluation, but AED treatment should not be withheld, even in patients with positive suicidal risks. When starting an AED or switching from one to other AEDs, patients should be advised to report to their treating physician any change in mood and suicidal ideation. Data on treatment-emergent psychiatric adverse events need to be collected, in addition to general safety information, during controlled studies in order to have meaningful information for patients and their relatives when a new drug is marketed.


Economic analysis of physical activity interventions.
Numerous interventions have been shown to increase physical activity but have not been ranked by effectiveness or cost. This study provides a systematic review of physical activity interventions and calculates their cost-effectiveness ratios. A systematic literature review was conducted (5579 articles) and 91 effective interventions promoting physical activity were identified, with enough information to translate effects into MET-hours gained. Cost-effectiveness ratios were then calculated as cost per MET-hour gained per day per individual reached. Physical activity benefits were compared to U.S. guideline-recommended levels (1.5 MET-hours per day for adults and 3.0 MET-hours per day for children, equivalent to walking 30 and 60 minutes, respectively). The most cost-effective strategies were for point-of-decision prompts (e.g., signs to prompt stair use), with a median cost of $0.07/MET-hour/day/person; these strategies had tiny effects, adding only 0.2% of minimum recommended physical activity levels. School-based physical activity interventions targeting children and adolescents ranked well with a median of $0.42/MET-hour/day/person, generating an average of 16% of recommended physical activity. Although there were few interventions in the categories of "creation or enhanced access to places for physical activity" and "community campaigns," several were cost effective. The least cost-effective categories were the high-intensity "individually adapted behavior change" and "social support" programs, with median cost-effectiveness ratios of $0.84 and $1.16 per MET-hour/day/person. However, they also had the largest effect sizes, adding 35%-43% of recommended physical activity, respectively. Study quality was variable, with many relying on self-reported outcomes. The cost effectiveness, effect size, and study quality should all be considered when choosing physical activity interventions.


Community interventions providing care and support to orphans and vulnerable children: a review of evaluation evidence.
Children affected by HIV in their families and communities face multiple risks to their health, education and psychosocial wellbeing. Community interventions for children who have been orphaned or rendered vulnerable take many forms, including educational assistance, home-based care, legal protection and psychosocial support. Despite a recent influx of funding for programme implementation, there exists little evidence to inform policymakers about whether their investments are improving the lives of vulnerable children and meeting key benchmarks including the Millennium Development Goals. This paper reviews the current evidence base on evaluations of community interventions for orphans and vulnerable children (OVC) in high HIV-prevalence African settings, focusing on studies' methodologies. Sources reviewed include published research studies and evidence from the unpublished programmatic "grey literature" located through database and internet searches. A total of 21 studies, varying in scope and generalisability, were identified. Interventions reviewed address children's wellbeing through various strategies within their communities. Evaluation methodologies reflect quantitative and qualitative approaches, including surveys (with and without baseline or comparison data), costing studies, focus groups, interviews, case studies, and participatory review techniques. Varied study methodologies reflect diverse research questions, various intervention types, and the challenges associated with evaluating complex interventions; highlighting the need to broaden the research paradigm in order to build the evidence base by including quasi-experimental and process evaluation approaches, and seeking further insights through participatory qualitative methodologies and costing studies. Although findings overall indicate the value of community interventions in effecting measurable improvements in child and family wellbeing, the quality and rigour of evidence is varied. A strategic research agenda is urgently needed to inform resource allocation and programme management decisions. Immediate imperatives include building local technical capacity to conduct quantitative and qualitative evaluation research, and strengthening monitoring and evaluation systems to collect process and outcome data (including costing) on key support models. Donors and implementers must support the collection of sound empirical evidence to inform the development and scale-up of OVC programmes.


Area deprivation affects behavioral problems of young adolescents in mixed urban and rural areas: the TRAILS study.
Behavioral problems occur more frequently among adolescents in deprived areas, but most evidence concerns urbanized areas. Our aim was to assess the impact of area deprivation and urbanization on the occurrence and development of behavioral problems among adolescents in a mixed urban and rural area and to examine the contributory factors. We obtained data from the first two waves (n=2,230; mean ages, 11.5 and 13.5 years respectively; response at follow-up, 96.4%) of the TRacking Adolescents' Individual Lives Survey (TRAILS). TRAILS is a prospective study of adolescent mental health in a mixed urban and rural region of the Netherlands. We assessed adolescent behavioral problems using the parent-reported Child Behavior Checklist (CBCL), the adolescent-reported Youth Self-Report (YSR) and the Antisocial Behavior Scale (ABS). Living areas were categorized into tertiles of deprivation. We further collected data on child temperament, perceived rearing style, parental socioeconomic position (education, income and occupation), family composition, and parental mental health history. At baseline, adolescents living in the most deprived tertile more frequently had elevated behavioral problem scores than those from the least deprived tertile on the CBCL (11.2% against 7.1%), YSR (11.9% against 6.9%), and ASB (11.5% against 7.4%) (all p < .05). Socioeconomic position explained half of the differences due to area deprivation. Other familial and parental characteristics did not significantly contribute to the explanation of observed area differences. As in highly urbanized areas, behavioral problems occur more frequently among adolescents in deprived mixed rural and urban areas. Urbanization has little effect on these area differences.


Regulation of memory - from the adrenal medulla to liver to astrocytes to neurons.
Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, resulting in increased blood glucose levels. The increase in blood glucose provides additional energy substrates to the brain to buttress the processes needed for an experience to be learned and remembered. In part, it appears that the increased glucose may act in the brain in a manner akin to that evident in the liver, engaging glycogenolysis in astrocytes to provide an energy substrate, in this case lactate, to augment neuronal functions. Together, the findings reveal a mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes. This article is part of a Special Issue entitled 'Memory enhancement'.


The provision of innervated skin cover for the injured thumb using dorsal metacarpal artery island flaps.
Provision of stable sensate skin is of great importance in reconstruction of the injured thumb. Island flaps based on the dorsal metacarpal arteries were used to resurface ten injured thumbs, and the degree of retained sensibility was assessed using static and moving two-point discrimination and the pick-up test. Results show that these flaps are capable of providing stable full-thickness skin cover in a single procedure and functional sensibility is retained in most cases. The second dorsal metacarpal artery island flap, previously advocated for use in small thumb defects only, has been successfully used as a large wraparound flap in two cases. In one of these it was used with free bone graft to increase the length of the thumb and an excellent functional result was achieved.


Release of bacterial DNA by marine nanoflagellates, an intermediate step in phosphorus regeneration.
The concentrations of dissolved DNA and nanoflagellates were found to covary during a study of diel dynamics of the microbial food web in the Adriatic Sea. This observation was further investigated in a continuous seawater culture when nanoflagellates were fed bacteria grown in filtered seawater. Analysis of dissolved organic phosphorus and dissolved DNA showed a sixfold increase of dissolved DNA in the presence of the nanoflagellates (Ochromonas sp.). The amount of DNA released suggested that the majority of the consumed bacterial DNA was ejected. Phagotrophic nanoflagellates thus represent an important source of origin for dissolved DNA. The rate of breakdown of dissolved DNA and release of inorganic phosphorus in the pelagic ecosystem is suggested to be dependent on the ambient phosphate pool. In the P-limited northern Adriatic Sea, rapid degradation of the labelled DNA could be demonstrated, whereas the N-limited southern California bight water showed a much lower rate. Phosphorus originating from dissolved DNA was shown to be transferred mainly to organisms in the <3-mum-size fractions. On the basis of the C/P ratios, we suggest that a significant fraction of the phosphorus demand by the autotrophs may be sustained by the released DNA during stratified conditions. Thus, the nucleic acid-rich bacterial biomass grazed by protozoa plays an important role in the biogeochemical cycling of phosphorus in the marine environment.


The economics of ideas and intellectual property.
Innovation and the adoption of new ideas is fundamental to economic progress. Here we examine the underlying economics of the market for ideas. From a positive perspective, we examine how such markets function with and without government intervention. From a normative perspective, we examine the pitfalls of existing institutions, and how they might be improved. We highlight recent research by us and others challenging the notion that government awards of monopoly through patents and copyright are "the way" to provide appropriate incentives for innovation.


Costs per discharge and hospital ownership under prospective payment and cost-based reimbursement systems in Taiwan.
This study in Taiwan examined the relationships between health care costs and hospital ownership under two financing systems with diametrically opposite incentives, case-payment (a form of prospective payment) and cost-based reimbursement. The universal sample of patients treated in 2000, for three standard care groups under each payment method, was included. The case payment diagnoses were uncomplicated cases of caesarean section, femoral/inguinal hernia operation and thyroidectomy, and the cost-based reimbursement diagnoses were uncomplicated cases of benign breast neoplasm, pneumococcal pneumonia and traumatic finger amputation. Costs per discharge were significantly lower in for-profit hospitals (by 2.8 to 5.7%) compared with public and not-for-profit hospitals for case payment diagnoses, which is consistent with the literature on US hospitals. For the cost-based reimbursement diagnoses, for-profits had 11.5 to 21.8% higher costs per discharge. The opposite direction of associations under the two payment systems validates the assumptions of the property rights theory in Taiwan's health care sector. Three plausible explanations for the study findings are suggested: (1). greater productive efficiency in private hospitals under case payment, (2). cost shifting from case payment diagnoses to cost-reimbursed diagnoses, and (3). patient dumping. Longitudinal studies using detailed hospital-level information with patient tracking facility are needed to clarify these issues.


Cluster-based network modeling-From snapshots to complex dynamical systems.
We propose a universal method for data-driven modeling of complex nonlinear dynamics from time-resolved snapshot data without prior knowledge. Complex nonlinear dynamics govern many fields of science and engineering. Data-driven dynamic modeling often assumes a low-dimensional subspace or manifold for the state. We liberate ourselves from this assumption by proposing cluster-based network modeling (CNM) bridging machine learning, network science, and statistical physics. CNM describes short- and long-term behavior and is fully automatable, as it does not rely on application-specific knowledge. CNM is demonstrated for the Lorenz attractor, ECG heartbeat signals, Kolmogorov flow, and a high-dimensional actuated turbulent boundary layer. Even the notoriously difficult modeling benchmark of rare events in the Kolmogorov flow is solved. This automatable universal data-driven representation of complex nonlinear dynamics complements and expands network connectivity science and promises new fast-track avenues to understand, estimate, predict, and control complex systems in all scientific fields.


Antitumour potential of a polysaccharide-rich substance from the fruit juice of Morinda citrifolia (Noni) on sarcoma 180 ascites tumour in mice.
An immunomodulatory polysaccharide-rich substance (Noni-ppt) from the fruit juice of Morinda citrifolia has been found to possess both prophylactic and therapeutic potentials against the immunomodulator sensitive Sarcoma 180 tumour system. The antitumour activity of Noni-ppt produced a cure rate of 25%-45% in allogeneic mice and its activity was completely abolished by the concomitant administration of specific inhibitors of macrophages (2-chloroadenosine), T cells (cyclosporine) or natural killer (NK) cells (anti-asialo GM1 antibody). Noni-ppt showed synergistic or additive beneficial effects when combined with a broad spectrum of chemotherapeutic drugs, including cisplatin, adriamycin, mitomycin-C, bleomycin, etoposide, 5- fl uorouracil, vincristine or camptothecin. It was not beneficial when combined with paclitaxel, cytosine arabinoside, or immunosuppressive anticancer drugs such as cyclophosphamide, methotrexate or 6-thioguanine. Noni-ppt also demonstrated beneficial effects when combined with the Th1 cytokine, interferon gamma, but its activity was abolished when combined with Th2 cytokines, interleukin-4 or interleukin-10, thereby suggesting that Noni-ppt induces a Th1 dominant immune status in vivo. The combination of Noni-ppt with imexon, a synthetic immunomodulator, also demonstrated beneficial effects, but not when combined with the MVE-2 copolymer, a high molecular weight immunomodulator. It was also not effective when combined with interleukin-2 or interleukin-12.


Asn-Trp dipeptides improve the oxidative stress and learning dysfunctions in D-galactose-induced BALB/c mice.
The oral administration of Asn-Trp (NW) or carnosine (β-alanyl-L-histidine) dipeptides to D-galactose (Gal)-induced BALB/c mice was used to evaluate antioxidant activities in vivo. D-Galactose (Gal) was subcutaneously injected into the dorsal necks of mice daily for eight weeks to induce oxidative stress (Gal group). From the beginning of the fifth week, groups of NW10, NW40 (10 or 40 mg NW kg(-1)) or carnosine40 (40 mg carnosine kg(-1)) were administered orally concurrent Gal injection until the end of studies. It was found that the malondialdehyde (MDA) contents in these intervention groups were much lower than the Gal group. The mice in the NW40 group showed significant improvements compared to the Gal group in a reference memory task and probe trial test evaluated by Morris water maze. Mice in the intervention groups showed higher GSH levels and oxygen radical antioxidant capacity activities and lower MDA levels in the brain or liver tissues compared to the Gal group. The levels of advanced glycation end-products, including N(ε)-(carboxymethyl)lysine (CML) and argpyrimidine, in the brain tissues of the NW40 interventions are significantly lower compared to the Gal group. These results suggest that NW may be useful in developing functional foods for antioxidant and anti-aging purposes.


Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation.
We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated.


Improvements in survival and disparities for advanced-stage laryngeal cancer.
Laryngeal cancer survival rates have declined over the past 2 decades. Primary surgical therapy may increase survival rates in advanced-stage tumors. To compare survival outcomes for initial surgical treatment of advanced-stage primary tumors in the Louisiana health system with outcomes in the National Cancer Database (NCDB). Retrospective analysis was conducted at an academic tertiary referral hospital. Patients diagnosed as having laryngeal carcinoma between 1998 and 2007 were identified via a tumor registry. Louisiana State University Health-Shreveport (LSU Health) data and national data from 2000 to 2010 were obtained from the NCDB of the American College of Surgeons. Treatment of laryngeal cancer. Age, sex, race/ethnicity, socioeconomic status, laryngeal subsite, stage, primary treatment modality, and observed survival were analyzed and compared. A total of 165 patients treated at LSU Health met the inclusion criteria. One hundred seventeen (70.91%) presented with advanced-stage (III/IV) disease, compared with 46.67% nationwide (P < .01). For stage IV disease our 5-year survival rate was 55.54% (95% CI, 43.35%-66.11%)compared with 31.60% (95% CI, 30.40%-32.90%) nationally (P < .05). Our proportion of uninsured patients was 23.73% vs 5.05% of patients nationally (P < .001), and our patients traveled further distances for care with 60.47% traveling 50 miles or more, compared with 15.87% nationally (P < .001). Sixty-four of the patients with advanced-stage disease (54.70%) underwent primary surgical therapy to include total laryngectomy. Data from the NCDB indicate that the rate of laryngectomy declined from 40% to 60% in the 1980s to 32% in 2007. Louisiana State University Health-Shreveport treated more uninsured patients with advanced-stage laryngeal cancer compared with national data but demonstrated higher survival rates for those with advanced-stage disease. The results also demonstrate that we have continued a high rate of primary surgical therapy for advanced-stage disease, despite the national trend toward organ preservation. We believe that upfront laryngectomy may explain our higher survival rates for advanced-stage laryngeal cancer.


The effect of the brain-type natriuretic peptide single-nucleotide polymorphism rs198389 on test characteristics of common assays.
To assess in a US general adult population the effect of the functional single-nucleotide polymorphism rs198389 in the promoter region of the gene of brain-type natriuretic peptide (BNP) on 3 commonly used BNP assays, clinical phenotype, disease prevalence, overall survival, and diagnostic test characteristics of BNP as a biomarker. We genotyped for rs198389 in a random sample of the general population (aged ≥ 45 years; n = 1970; enrolled between June 1, 1997, and September 30, 2000) from Olmsted County, Minnesota. Patients were characterized biochemically, clinically, echocardiographically, and regarding BNP molecular forms (2 assays for BNP and 1 assay for amino-terminal proBNP). Median follow-up was 9 years. Genotype frequencies were in Hardy-Weinberg equilibrium (P = .98): TT genotype, n = 645 (32.7%); TC genotype, n = 983 (49.9%); and CC genotype, n = 342 (17.4%). The C allele independently predicted higher BNP forms (P<.001 for all assays). Genotypes did not differ with regard to clinical and echocardiographic phenotype or overall survival. When previously reported genotype-unadjusted cut points for the detection of left ventricular ejection fraction less than or equal to 40% (n = 37 [1.9%]) and less than or equal to 50% (n = 116 [6.0%]) were used, sensitivity generally increased with the number of C alleles, whereas specificity decreased, both on average by more than 10% for the TT vs CC genotype. The C allele of rs198389 is common in the general US population and is associated with higher concentrations of BNP molecular forms but not with cardiovascular phenotype or survival. The C allele confounds the test characteristics of commonly used assays.


Clinical response to radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.
Radium-223 prolongs survival and decreases symptomatic skeletal events in men with metastatic castrate-resistant prostate cancer and is indicated in patients with painful bone metastases. However, pain responses are rarely reported and often asked about by patients. Further, patients and their physicians are concerned about a lack of pain response portending a poor treatment response and may be inclined to change systemic therapies before completing 6 cycles. We evaluated the likelihood and time course of pain response, potential predictors of response, and its prognostic value in patients receiving radium-223. We reviewed the charts of patients who received radium-223 in our department. All patients were planned for 6 cycles with a prescribed dose of 50-55 kBq/kg at each administration. Pain scores, subjective response to pain, analgesic use, treatment toxicities, and laboratory values were recorded at each visit. Symptomatic skeletal events and survival were also recorded. 48 patients received at least one cycle of radium-223 and 27 (56%) received all 6 planned cycles. Median survival from first treatment was 16.0 months (95% CI 8.9 to 19.2 months). 33% experienced at least one symptomatic skeletal event during or after treatment. 62.5% of men reported a decrease in pain from pre-treatment baseline. Of men with improved pain, 96% experienced an improvement before the third cycle. Pain relief was not associated with a decrease in ALK-P or PSA or improved survival. Approximately two-thirds of patients who undergo treatment with radium-223 will experience an improvement in pain and, if it occurs, it will most likely occur within the first two cycles. Patients should be counseled about this timeline and, if pain improvement isn't achieved, palliative radiation and oral analgesic readjustment should be considered. Pain response is not associated with survival and should not be used to evaluate the effectiveness of treatment.


Adding video-debriefing to Helping-Babies-Breathe training enhanced retention of neonatal resuscitation knowledge and skills among health workers in Uganda: a cluster randomized trial.
Skilled birth attendants must be competent to provide prompt resuscitation to save newborn lives at birth. Both knowledge and skills (competence) decline with time after training but the optimal duration for refresher training among frontline-skilled birth attendants in low-resource settings is unknown. We assessed the effect of an innovative Helping-Babies-Breathe simulation-based teaching method using video-debriefing compared to standard Helping-Babies-Breathe training on 1) neonatal resuscitation knowledge and skills attainment and 2) competence retention among skilled birth attendants in Northern Uganda. A total of 26 health facilities with 86 birth attendants were equally randomised to intervention and control arms. The 2nd edition of the American Association of Pediatrics Helping-Babies-Breathe curriculum was used for training and assessment. Knowledge and skills were assessed pre- and post-training, and during follow-up at 6 months. A mixed effects linear regression model for repeated measures was used to assess the short and long-term effects of the intervention on neonatal resuscitation practices while accounting for clustering. Eighty-two (95.3%) skilled birth attendants completed follow-up at 6 months. Approximately 80% of these had no prior Helping-Babies-Breathe training and 75% reported practicing neonatal resuscitation routinely. Standard Helping-Babies-Breathe training with video-debriefing improved knowledge and skills attainment post-training [adjusted mean difference: 5.34; 95% CI: 0.82-10.78] and retention [adjusted mean difference: 2.97; 95% CI: 1.52-4.41] over 6 months post-training compared to standard training after adjusting for confounding and clustering. Factors that reduced knowledge and skills retention among birth attendants were monthly resuscitation of one neonate or more and being in service for more than 5 years. Adding video-debriefing to standard Helping-Babies-Breathe training had an effect on birth attendants' competence attainment and retention over 6 months in Uganda. However, more research is needed to justify the proposed intervention in this context.


Opening an electrical band gap of bilayer graphene with molecular doping.
The opening of an electrical band gap in graphene is crucial for its application for logic circuits. Recent studies have shown that an energy gap in Bernal-stacked bilayer graphene can be generated by applying an electric displacement field. Molecular doping has also been proposed to open the electrical gap of bilayer graphene by breaking either in-plane symmetry or inversion symmetry; however, no direct observation of an electrical gap has been reported. Here we discover that the organic molecule triazine is able to form a uniform thin coating on the top surface of a bilayer graphene, which efficiently blocks the accessible doping sites and prevents ambient p-doping on the top layer. The charge distribution asymmetry between the top and bottom layers can then be enhanced simply by increasing the p-doping from oxygen/moisture to the bottom layer. The on/off current ratio for a bottom-gated bilayer transistor operated in ambient condition is improved by at least 1 order of magnitude. The estimated electrical band gap is up to ∼111 meV at room temperature. The observed electrical band gap dependence on the hole-carrier density increase agrees well with the recent density-functional theory calculations. This research provides a simple method to obtain a graphene bilayer transistor with a moderate on/off current ratio, which can be stably operated in air without the need to use an additional top gate.


Stress management in the treatment of mild primary hypertension.
The use of simple relaxation-based stress management procedures in the treatment of mild primary hypertension has been the subject of extensive study. Stress management appears to lead to reliably greater reductions in pressure than a variety of control procedures. The mechanisms underlying these effects are obscure, and research has not identified which patients will benefit most from treatment. Preliminary data suggest that stress management may reduce the risk of coronary heart disease, but much research must be done if this is to be confirmed. It is suggested that such research should take into account the possibility that stress management may have beneficial effects on more than just hypertension-related aspects of the cardiovascular disease process.


Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial.
Nosocomial pneumonia due to antimicrobial-resistant pathogens is associated with high mortality. We assessed the efficacy and safety of the combination antibacterial drug ceftolozane-tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia. We conducted a randomised, controlled, double-blind, non-inferiority trial at 263 hospitals in 34 countries. Eligible patients were aged 18 years or older, were undergoing mechanical ventilation, and had nosocomial pneumonia (either ventilator-associated pneumonia or ventilated hospital-acquired pneumonia). Patients were randomly assigned (1:1) with block randomisation (block size four), stratified by type of nosocomial pneumonia and age (<65 years vs ≥65 years), to receive either 3 g ceftolozane-tazobactam or 1 g meropenem intravenously every 8 h for 8-14 days. The primary endpoint was 28-day all-cause mortality (at a 10% non-inferiority margin). The key secondary endpoint was clinical response at the test-of-cure visit (7-14 days after the end of therapy; 12·5% non-inferiority margin). Both endpoints were assessed in the intention-to-treat population. Investigators, study staff, patients, and patients' representatives were masked to treatment assignment. Safety was assessed in all randomly assigned patients who received study treatment. This trial was registered with ClinicalTrials.gov, NCT02070757. Between Jan 16, 2015, and April 27, 2018, 726 patients were enrolled and randomly assigned, 362 to the ceftolozane-tazobactam group and 364 to the meropenem group. Overall, 519 (71%) patients had ventilator-associated pneumonia, 239 (33%) had Acute Physiology and Chronic Health Evaluation II scores of at least 20, and 668 (92%) were in the intensive care unit. At 28 days, 87 (24·0%) patients in the ceftolozane-tazobactam group and 92 (25·3%) in the meropenem group had died (weighted treatment difference 1·1% [95% CI -5·1 to 7·4]). At the test-of-cure visit 197 (54%) patients in the ceftolozane-tazobactam group and 194 (53%) in the meropenem group were clinically cured (weighted treatment difference 1·1% [95% CI -6·2 to 8·3]). Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure. Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane-tazobactam group and 27 (8%) of 359 in the meropenem group. Eight (2%) patients in the ceftolozane-tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events. There were no treatment-related deaths. High-dose ceftolozane-tazobactam is an efficacious and well tolerated treatment for Gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population. Merck & Co.


Saliva-activated transmission (SAT) of Thogoto virus: dynamics of SAT factor activity in the salivary glands of Rhipicephalus appendiculatus, Amblyomma variegatum, and Boophilus microplus ticks.
Thogoto (THO) virus is transmitted from infected to uninfected ticks when co-feeding on uninfected guinea-pigs, even though the guinea-pigs do not develop a detectable viraemia. This form of non-viraemic transmission is potentiated by a factor(s) secreted by the saliva of ticks and hence has been termed saliva-activated transmission (SAT). The synthesis of the SAT factor by the salivary glands of three ixodid tick species was determined by placing uninfected nymphal ticks on guinea-pigs that were subsequently inoculated with a mixture of THO virus and salivary gland extract (SGE) derived from one of the tick species. SAT factor activity was measured by determining the number of nymphs that acquired THO virus. For the three-host ixodid species, Rhipicephalus appendiculatus and Amblyomma variegatum, maximum enhancement of THO virus transmission was observed when salivary glands were derived from uninfected female ticks that had fed for a period of 6 or 8 days, respectively. In contrast, when salivary glands were derived form uninfected female Boophilus microplus, a one-host ixodid tick species, enhancement of THO virus transmission was observed throughout the tick feeding period. Thus, the natural feeding behaviour of ticks appears to be an important factor in determining the relative importance of these vectors in mediating SAT.


Authentic tart cherry juice reduces markers of inflammation in overweight and obese subjects: a randomized, crossover pilot study.
Subclinical inflammation is frequently noted in chronic diseases such as diabetes, cardiovascular disease (CVD) and obesity. Accumulating epidemiological evidence demonstrates that diets rich in vegetables and fruits, e.g., cherries, may significantly reduce the risk of chronic disease, in part, via antioxidant and anti-inflammatory activities. In this randomized, placebo-controlled crossover study, we recruited 10 at-risk participants (38.1 ± 12.5 years; 8 females, 2 males) with BMI >25.0 kg m-2 (32.2 ± 4.6 kg m-2; 5 obese, 5 overweight) to consume 240 mL (8 ounces) daily of either 100% tart cherry juice (TCJ) or an alternate placebo beverage, for 4 weeks with a 2-week intervening washout period before switching to the alternate beverage for four weeks. Fasting blood samples were collected at the beginning and end of each arm for measurement of biomarkers of inflammation. The erythrocyte sedimentation rate (ESR), an indicator of chronic inflammation, was significantly (p < 0.05) lower with TCJ than with the placebo beverage, which increased ESR by 19%. Mean baseline hsCRP, an indicator of acute inflammation, was 7.0 ± 5.2 mg L-1 and consumption of TCJ did not affect hsCRP levels. The chemokine MCP-1 and cytokine TNF-alpha were lower in participants after consuming TCJ compared to those consuming the placebo beverage. Plasma IL-6 and IL-l0 were not different between treatments. Collectively, the data suggest that authentic 100% TCJ may reduce biomarkers of inflammation often noted in chronic disease and may be a preferable dietary selection compared to artificially flavored beverages with added sugars.


Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.
The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.


Cecal ligation and puncture-induced murine sepsis does not cause lung injury.
The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die after cecal ligation and puncture-induced sepsis compared with those predicted to live. Prospective, laboratory controlled experiments. University research laboratory. Adult, female, outbred Institute of Cancer Research mice. Mice underwent cecal ligation and puncture to induce sepsis. Two groups of mice were euthanized at 24 and 48 hrs postcecal ligation and puncture and samples were collected. These mice were further stratified into groups predicted to die (Die-P) and predicted to live (Live-P) based on plasma interleukin-6 levels obtained 24 hrs postcecal ligation and puncture. Multiple measures of lung inflammation and lung injury were quantified in these two groups. Results from a group of mice receiving intratracheal normal saline without surgical intervention were also included as a negative control. As a positive control, bacterial pneumonia was induced with Pseudomonas aeruginosa to cause definitive lung injury. Separate mice were followed for survival until Day 28 postcecal ligation and puncture. These mice were used to verify the interleukin-6 cutoffs for survival prediction. After sepsis, both the Die-P and Live-P mice had significantly suppressed measures of respiratory physiology but maintained normal levels of arterial oxygen saturation. Bronchoalveolar lavage levels of pro- and anti-inflammatory cytokines were not elevated in the Die-P mice compared with the Live-P. In addition, there was no increase in the recruitment of neutrophils to the lung, pulmonary vascular permeability, or histological evidence of damage. In contrast, all of these pulmonary injury and inflammatory parameters were increased in mice with Pseudomonas pneumonia. These data demonstrate that mice predicted to die during sepsis have no significant lung injury. In murine intra-abdominal sepsis, pulmonary injury cannot be considered the etiology of death in the acute phase.


Risk assessment and management in bipolar disorders.
Bipolar affective disorders carry significant risks to the patient and sometimes others. The form of the illness relapse needs to be determined, and high-risk features such as psychosis and suicide considered. Gathering collateral information from others is invaluable. Mania brings particular risks of disinhibition, poor judgement, risk taking and sometimes aggression. Depression carries notable risks of suicidal behaviour, poor self-care and homicide. Both mania and depression bring risks of substance misuse and disrupted relationships. Management requires an optimal therapeutic alliance with good communication, appropriate treatment and sometimes compulsory care during crises. Preventive strategies are invaluable.


A Rhizobium meliloti lipopolysaccharide mutant altered in competitiveness for nodulation of alfalfa.
A transposon Tn5-induced mutant of Rhizobium meliloti Rm2011, designated Rm6963, showed a rough colony morphology on rich and minimal media and an altered lipopolysaccharide (LPS). Major differences from the wild-type LPS were observed in (i) hexose and 2-keto-3-deoxyoctonate elution profiles of crude phenol extracts chromatographed in Sepharose CL-4B, (ii) silver-stained sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis patterns of crude and purified LPS fractions, and (iii) immunoreactivities otherwise present in purified LPS of the parental strain Rm2011. In addition, Rm6963 lost the ability to grow in Luria-Bertani medium containing the hydrophobic compounds sodium deoxycholate or SDS and showed a decrease in survival in TY medium supplemented with high calcium concentrations. The mutant also had altered symbiotic properties. Rm6963 formed nodules that fixed nitrogen but showed a delayed or even reduced ability to nodulate the primary root of alfalfa without showing changes in the position of nodule distribution profiles along the roots. Furthermore, 2 to 3 weeks after inoculation, plants nodulated by Rm6963 were smaller than control plants inoculated with wild-type bacteria in correlation with a transient decrease in nitrogen fixation. In most experiments, the plants recovered later by expressing a full nitrogen-fixing phenotype and developing an abnormally high number of small nodules in lateral roots after 1 month. Rm6963 was also deficient in the ability to compete for nodulation. In coinoculation experiments with equal bacterial numbers of both mutant and wild-type rhizobia, only the parent was recovered from the uppermost root nodules. A strain ratio of approximately 100 to 1 favoring the mutant was necessary to obtain an equal ratio (1:1) of nodule occupancy. These results show that alterations in Rm6963 which include LPS changes lead to an altered symbiotic phenotype during the association with alfalfa that affects the timing of nodule emergence, the progress of nitrogen fixation, and the strain competitiveness for nodulation.


Integrating psychosocial care into neuro-oncology: challenges and strategies.
Approximately 256,000 cases of malignant brain and nervous system cancer were diagnosed worldwide during 2012 and 189,000 deaths, with this burden falling more heavily in the developed world. Problematically, research describing the psychosocial needs of people with brain tumors and their carers and the development and evaluation of intervention models has lagged behind that of more common cancers. This may relate, at least in part, to poor survival outcomes and high morbidity associated with this illness, and stigma about this disease. The evidence base for the benefits of psychosocial care in oncology has supported the production of clinical practice guidelines across the globe over the past decade, with a recent mandate to integrate the psychosocial domain and measurement of distress into routine care. Clinical care guidelines for people with brain tumors have emerged, with a building focus on psychosocial and survivorship care. However, researchers will need to work intensively with health care providers to ensure future practice is evidence-based and able to be implemented across both acute and community settings and likely within existing resources.


A ray analysis of optical resonators formed by two spherical mirrors.
A paraxial resonance equation is derived. This gives the mirror separation as a function of the radii of curvature of the mirrors and an integer N which is the number of return transits necessary to form a closed path of rays. Differentiating the paraxial resonance equation gives a formula for the relative mode density as a function of mirror separation. It is shown that the output power from a laser incorporating solid mirrors is inversely proportional to the mode density. In the case of hole coupling, the output power follows the same general profile but dips in power occur at the mirror separations corresponding to the resonance configurations of modes characterized by low values of N. Further confirmation of the paraxial resonance equation is obtained from passive resonators in which conic interference fringes and sudden increases in transmitted intensity are found to occur at the predicted mirror separations for low values of N corresponding to mode-degenerate configurations. The positions of the vertices of the ray traces are found to correspond to the patterns of discrete spots which are obtained in the output of a CO(2) laser incorporating Brewster angle windows and a solid germanium mirror. The laser configurations which give maximum output power are plotted as a cliff of constant height above the g(1)g(2) plane of the stability diagram, where g(1) and g(2) are the configuration coordinates. The relative merits of all possible cavity configurations having one mirror in common are shown as a set of equipower contours, and the hyperbolic curves of constant N are also superimposed on the stability diagram. The advantages of simplicity and directness in using the ray model are made clear.


Cognitive Therapy for Social Anxiety Disorder in Adolescents: A Development Case Series.
Social anxiety disorder is common and typically starts in childhood or adolescence. Cognitive Therapy for Social Anxiety Disorder (CT-SAD) in adults is a well-established treatment that shows strong evidence of differential effectiveness when compared to other active treatments. In contrast, CBT approaches to social anxiety in young people have yet to demonstrate differential effectiveness and there is some evidence that young people with social anxiety disorder respond less well than those with other anxiety disorders. To adapt CT-SAD for use with adolescents and conduct a pilot case series. Five adolescents, aged 11-17 years, with a primary DSM-5 diagnosis of social anxiety disorder received a course of CT-SAD adapted for adolescents. Standardized clinical interview and questionnaire assessments were conducted at pre and posttreatment, and 2 to 3-month follow-up. All five participants reported severe social anxiety at baseline and achieved remission by the end of treatment. Significant improvements were also observed in general anxiety, depression, concentration in the classroom, and putative process measures (social anxiety related thoughts, beliefs and safety behaviours). An adapted form of CT-SAD shows promise as a treatment for adolescents.


Development of a Model to Predict 10-Year Risk of Ischemic and Hemorrhagic Stroke and Ischemic Heart Disease Using the China Kadoorie Biobank.
Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China. We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration. Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women. Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population. This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30-79 years.


Origin of the anomalous Fe-CO stretching mode in the CO complex of Ascaris hemoglobin.
We report an unusually high frequency (543 cm(-)(1)) for an Fe-CO stretching mode in the CO complex of Ascaris suum hemoglobin as compared to vertebrate hemoglobins in which the frequency of the Fe-CO mode is much lower. A second Fe-CO stretching mode in Ascaris hemoglobin is observed at 515 cm(-1). We propose that these two Fe-CO stretching modes arise from two protein conformers corresponding to interactions of the heme-bound CO with the B10-tyrosine or the E7-glutamine residues. This postulate is supported by spectra from the B10-Tyr --> Phe mutant in which the 543 cm(-1) line is absent. Thus, a strong polar interaction, such as hydrogen bonding, of the CO with the distal B10 tyrosine residue is the dominant factor that causes this anomalously high frequency. Strong hydrogen bonding between O(2) and distal residues in the oxy complex of Ascaris hemoglobin has been shown to result in a rigid structure, rendering an extremely low oxygen off rate [Gibson, Q. H., and Smith, M. H. (1965) Proc. R. Soc. London B 163, 206-214]. In contrast, the CO off rate in Ascaris hemoglobin is very similar to that in sperm whale myoglobin. The high CO off rate relative to that of O(2) in Ascaris hemoglobin is attributed to a rapid equilibrium between the two conformations of the protein in the CO adduct, with the off rate being determined by the conformer with the higher rate.


Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.
The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw. Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. Ministry of Health, Brazil.


Appropriateness of Transcatheter Aortic Valve Replacement: Insight From the OCEAN-TAVI Registry.
Transcatheter aortic valve replacement (TAVR) is widely used; however, its appropriateness is unknown. We sought to investigate the appropriateness of TAVR. We assigned appropriateness ratings to patients undergoing TAVR for severe aortic stenosis between October 2013 and May 2017 at 14 Japanese hospitals participating in the optimized transcatheter valvular intervention-transcatheter aortic valve implantation registry according to the US appropriate use criteria for treating severe aortic stenosis. To account for the influence of uncaptured variables on appropriate use criteria ratings, we initially assigned them to a best-case scenario where they were assumed to classify a case to the most appropriate clinical scenario and then to a worst-case scenario where assumed least appropriate. Overall proportion of TAVRs classified as appropriate, maybe appropriate, or rarely appropriate was assessed. In addition, extent of hospital-level variation in rarely appropriate procedures was evaluated. Of 2036 TAVRs (median age [25th, 75th]: 85.0 years [81.0-88.0]; 70.5% female the Society of Thoracic Surgeons Predicted Risk of Mortality score: 6.2% [4.4-8.9]), in the best-case scenario, 177 (8.7%) were not successfully mapped, and 1580 (77.6%) were classified as appropriate, 180 (8.8%) as maybe appropriate, 99 (4.9%) as rarely appropriate, respectively. In the worst-case scenario, the rate of rarely appropriate increased to 6.8%. The majority of rarely appropriate TAVRs was performed in patients with moderate to severe dementia (defined as mini-mental status examination of ≤17), bicuspid aortic valve, or anticipated life expectancy <1 year. There was substantial variation in the proportion of rarely appropriate TAVR across hospitals (median rate of rarely appropriate: 4.9% [3.8-6.6] in the best-case scenario, P<0.001; 6.5% [5.6-8.6] in the worst-case scenario, P<0.001). In clinical practice, the proportion of rarely appropriate TAVRs ranged from 4.9% to 6.8% with substantial institutional variation. Our study elucidates common clinical scenarios deemed rarely appropriate and clarifies the potential targets of quality improvement. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000020423.


The Lari-Leuco Container: A Novel Collection Arena for Separating Insects Ascending or Descending From a Plant Foliage Sample.
Efficient separation of insects from plant material for quantification and collection is an important component of entomological research. This paper reports on a novel, easily replicable container designed to efficiently collect two different biological control agents dispersing from hemlock (Tsuga spp.) foliage infested with the invasive hemlock woolly adelgid (HWA), Adelges tsugae Annand (Hemiptera: Adelgidae). The container utilizes a simplified Berlese-style funnel design to collect Laricobius spp. (Coleoptera: Derodontidae) larvae dropping from the foliage into a removable bottom jar, a central jar to house the foliage sample, and a removable top jar to collect adult silver flies (Leucopis spp., Diptera: Chamaemyiidae) emerging from puparia on the twigs. The efficacy of two designs (with and without a funnel leading to the top collection jar) was evaluated using western hemlock [Tsuga heterophylla (Raf.) Sarg.] foliage naturally colonized with HWA and the two predator genera. All Laricobius larvae were effectively collected in the bottom jar, and the addition of an inverted funnel leading to the top collection jar increased the proportion of Leucopis flies reaching the target jar from 60% to 94%. This 'Lari-Leuco' container is presented as a research and motoring tool to benefit the integrated pest management program for HWA in eastern North America and for potential use in simultaneously separating ascending and descending life stages in other insect-plant or predator-prey systems.


A first prospective, randomized, double-blind, placebo-controlled clinical trial evaluating extracorporeal shock wave therapy for the treatment of Peyronie's disease.
Extracorporeal shock wave therapy (ESWT) is a conservative therapy for patients with Peyronie's disease (PD). To investigate the effects of ESWT in patients with PD. One hundred patients with a history of PD not >12 mo who had not had previous PD-related treatments were enrolled in a prospective, randomized, double-blind, placebo-controlled study. Patients were randomly allocated to either ESWT (n=50) or placebo (n=50). Erectile function (EF), pain during erection, plaque size, penile curvature, and quality of life (QoL) were assessed at baseline, at 12 wk, and at 24 wk follow-up. Four weekly treatment sessions were administered. Each ESWT session consisted of 2000 focused shock waves. For the placebo group, a nonfunctioning transducer was employed. EF was evaluated with the shortened version of the International Index of Erectile Function (IIEF-5), pain was evaluated with a visual analog scale (VAS; 0-10), plaque size was measured in cm(2), and penile curvature was measured in degrees. After 12 wk, mean VAS score, mean IIEF-5 score, and mean QoL score ameliorated significantly in patients receiving ESWT. Mean plaque size and mean curvature degree were unchanged in the ESWT group, while a slight increase was reported in the placebo group (p-value not significant vs baseline). After 24 wk, mean IIEF-5 score and mean QoL score were stable in the ESWT group, while mean VAS score was significantly lower when compared with baseline in both groups. Interestingly, after 24 wk, mean plaque size and mean curvature degree were significantly higher in the placebo group when compared with both baseline and ESWT values. The main limitations were that the QoL questionnaire was not validated, ED was not etiologically characterized, and inclusion criteria were restricted. In patients with PD, ESWT leads to pain resolution and ameliorates both EF and QoL.


Asymmetrical voltage response in resonant neurons shaped by nonlinearities.
The conventional impedance profile of a neuron can identify the presence of resonance and other properties of the neuronal response to oscillatory inputs, such as nonlinear response amplifications, but it cannot distinguish other nonlinear properties such as asymmetries in the shape of the voltage response envelope. Experimental observations have shown that the response of neurons to oscillatory inputs preferentially enhances either the upper or lower part of the voltage envelope in different frequency bands. These asymmetric voltage responses arise in a neuron model when it is submitted to high enough amplitude oscillatory currents of variable frequencies. We show how the nonlinearities associated to different ionic currents or present in the model as captured by its voltage equation lead to asymmetrical response and how high amplitude oscillatory currents emphasize this response. We propose a geometrical explanation for the phenomenon where asymmetries result not only from nonlinearities in their activation curves but also from nonlinearites captured by the nullclines in the phase-plane diagram and from the system's time-scale separation. In addition, we identify an unexpected frequency-dependent pattern which develops in the gating variables of these currents and is a product of strong nonlinearities in the system as we show by controlling such behavior by manipulating the activation curve parameters. The results reported in this paper shed light on the ionic mechanisms by which brain embedded neurons process oscillatory information.


N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons.
In the nervous system the influx of Ca2+ orchestrates multiple biochemical and electrical events essential for development and function. A major route for Ca2+ entry is through voltage-dependent calcium channels (VDCCs). It is becoming increasingly clear that the precise contribution VDCCs make to neuronal function depends not only upon their specific electrophysiological properties but also on their distribution over the nerve cell surface. One location where the presence of VDCCs may be critical is the dendritic spine, a structure known to be the major site of excitatory synaptic input. On spines, VDCCs are hypothesized to play an essential role in signal processing, learning, and memory. However, direct evidence for the presence of VDCCs on spines is lacking. Attempts to examine the distribution of VDCCs, or indeed any other components, on spines have been hampered since the size of many spines is close to the limits of resolution of conventional light microscopy. Using a new, biologically active, fluorescein conjugate of omega-conotoxin (Fl-omega-CgTx), a selective blocker of N-type VDCCs, and confocal microscopy, we have mapped the distributions of N-type VDCCs on live CA1 neurons in rat hippocampal slices. VDCCs were found on somata, throughout the dendritic arbor, and on dendritic spines in all hippocampal subfields. A comparison of three-dimensional reconstructions of structures labeled by Fl-omega-CgTx with those outlined by 1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil) or Lucifer yellow confirmed the presence of N-type VDCCs on dendritic spines. However, spine frequency on dendrites labeled with Fl-omega-CgTx was much lower than the spine frequency on dendrites labeled with Lucifer yellow or Dil, suggesting that some spines lack N-type VDCCs. These results offer the first direct evidence for the localization of any voltage-dependent channel on dendritic spines. The presence of N-type VDCCs on dendrites and their spines argues that these channels may participate in the generation of active Ca2+ conductances in distal dendrites, and is consistent with a role for spines as specialized compartments for concentrating Ca2+.


Using aluminum for scatter control in mammography: preliminary work using measurements of CNR and FOM.
Full-field digital mammography (FFDM) systems provide the current gold standard in mammographic examinations. Although FFDM provides the lowest mammographic doses, the radiation dose to the breast during mammographic examinations is still a concern. Thus, image quality optimization at the lowest dose is a major goal. In planar X-ray imaging, thin sheets of aluminum (Al) are used as filtration to reduce the number of low-energy X-ray photons reaching the patient. The goal of this work was to evaluate whether Al can be used in FFDM to remove scatter radiation from reaching the image detector, hence improving image quality. Doses were compared with the use of a grid. A Hologic Selenia mammographic unit was used to acquire images of two phantoms, namely, the ACR phantom and a Perspex phantom of 5 cm. Images were acquired using two tube voltages (kVp) and filter combinations under two exposure/dose conditions. Al sheets of various thicknesses were placed between the phantom and the image detector. Contrast-to-noise ratio (CNR) and figure of merit (FOM) values were measured and compared with images acquired using a grid. When a constant dose was delivered to the image detector, the highest CNR was achieved using a grid; however, the highest FOM values were achieved when using 0.05 mm thick Al sheets. This study successfully demonstrates that thin sheets of Al can be used in mammography examinations to reduce scattered radiation and improve image quality, as indicated by the measured CNR values. Given the limitations of this work, further kVp and target/filter combinations and various methods of image quality measurement need to be studied.


Laser Assisted Non-surgical Periodontal Therapy: A Double Blind, Randomized Clinical Trial.
The objective of this study was to examine potential benefits of using laser therapy for secular decontamination in conjunction with scaling and root planing in the treatment of chronic periodontitis. The study was performed on 173 teeth in 14 patients in a split-mouth design, one side received scaling and root planing followed by laser therapy using a carbon dioxide (CO2) laser with an ablative handpiece (test group); the contralateral side received scaling and root planing without laser (control group). Clinical and laboratory parameters were evaluated prior to treatment and at 3 and 6 months following therapy; clinical measurements were performed by two blinded examiners. The clinical parameters included measurement of gingival recession (REC), bleeding on probing (BOP), clinical attachment level (CAL), pocket depth (PD), furcation involvement (FUR), and tooth mobility (MOB). Laboratory testing to determine the levels of periodontal pathogens was performed using PCR techniques. The results of the study revealed statistically significant differences in clinical and laboratory parameters at 3 and 6 months after therapy for both test and control groups, but no significant difference was observed between the two groups. However, sites receiving laser therapy tended to show a greater decrease in probing depths, gain in clinical attachment level, and reduced bacterial levels. In conclusion, the overall results of the study suggest a potential benefit of using laser therapy in conjunction with scaling and root planing for the treatment of chronic periodontitis.


Lifestyle and mental health.
Mental health professionals have significantly underestimated the importance of lifestyle factors (a) as contributors to and treatments for multiple psychopathologies, (b) for fostering individual and social well-being, and (c) for preserving and optimizing cognitive function. Consequently, therapeutic lifestyle changes (TLCs) are underutilized despite considerable evidence of their effectiveness in both clinical and normal populations. TLCs are sometimes as effective as either psychotherapy or pharmacotherapy and can offer significant therapeutic advantages. Important TLCs include exercise, nutrition and diet, time in nature, relationships, recreation, relaxation and stress management, religious or spiritual involvement, and service to others. This article reviews research on their effects and effectiveness; the principles, advantages, and challenges involved in implementing them; and the forces (economic, institutional, and professional) hindering their use. Where possible, therapeutic recommendations are distilled into easily communicable principles, because such ease of communication strongly influences whether therapists recommend and patients adopt interventions. Finally, the article explores the many implications of contemporary lifestyles and TLCs for individuals, society, and health professionals. In the 21st century, therapeutic lifestyles may need to be a central focus of mental, medical, and public health.


Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia.
Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. To examine the prevalence and determinants of vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. We conducted a population based case-control study in Tasmania, Australia (latitude 41-43 degrees S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D </= 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case sample. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.


miR-187 induces apoptosis of SiHa cervical carcinoma cells by downregulating Bcl-2.
Cervical carcinoma is a life-threatening illness posing considerable danger to women's health. microRNAs (miRNAs) have been shown to regulate multiple cellular events, including growth and proliferation, and miR-187 is thought to regulate the growth and apoptosis of certain cell types. Our study focused on the influence of miR-187 on the growth, proliferation, and apoptosis of SiHa cervical carcinoma cells, and explored the mechanism behind its pro-apoptotic effect. miR-187 and control (scrambled) miRNA were synthesized with a standard protocol and lipofected into SiHa cells. Thiazolyl blue tetrazolium bromide assays and tests of caspase-3 activity were then performed to examine growth, proliferation, and apoptosis by flow cytometry. Small interfering RNA (siRNA) and an expression plasmid were synthesized for inhibition and overexpression of Bcl-2, respectively, and following their transfection, western blotting was used to examine Bcl-2 protein levels. Compared to transfection with control miRNA, miR-187 significantly reduced SiHa cell growth and decreased Bcl-2 expression. Increased translocation of phosphatidylserine and activation of caspase-3 were observed in miR-187-transfected cells. Moreover, inhibition of Bcl-2 enhanced the pro-apoptotic effect of this miRNA, while Bcl-2 overexpression had the opposite effect. miR-187 inhibits the growth and proliferation of SiHa cells, and induces their apoptosis via downregulation of Bcl-2. Bcl-2 represents a potential therapeutic target for cervical carcinoma.


Evaluation method for the potential functionome harbored in the genome and metagenome.
One of the main goals of genomic analysis is to elucidate the comprehensive functions (functionome) in individual organisms or a whole community in various environments. However, a standard evaluation method for discerning the functional potentials harbored within the genome or metagenome has not yet been established. We have developed a new evaluation method for the potential functionome, based on the completion ratio of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules. Distribution of the completion ratio of the KEGG functional modules in 768 prokaryotic species varied greatly with the kind of module, and all modules primarily fell into 4 patterns (universal, restricted, diversified and non-prokaryotic modules), indicating the universal and unique nature of each module, and also the versatility of the KEGG Orthology (KO) identifiers mapped to each one. The module completion ratio in 8 phenotypically different bacilli revealed that some modules were shared only in phenotypically similar species. Metagenomes of human gut microbiomes from 13 healthy individuals previously determined by the Sanger method were analyzed based on the module completion ratio. Results led to new discoveries in the nutritional preferences of gut microbes, believed to be one of the mutualistic representations of gut microbiomes to avoid nutritional competition with the host. The method developed in this study could characterize the functionome harbored in genomes and metagenomes. As this method also provided taxonomical information from KEGG modules as well as the gene hosts constructing the modules, interpretation of completion profiles was simplified and we could identify the complementarity between biochemical functions in human hosts and the nutritional preferences in human gut microbiomes. Thus, our method has the potential to be a powerful tool for comparative functional analysis in genomics and metagenomics, able to target unknown environments containing various uncultivable microbes within unidentified phyla.


Encounters in cancer treatment: intersubjective configurations of a need for rehabilitation.
Based on extensive ethnographic material from in-depth interviews with Danish cancer patients after treatment, this study analyzes their stories to explore how interactions with the physician configures and situates a need for rehabilitation. We identify three themes in the illness stories: (1) attentiveness and care; (2) fragmentation and objectification; and (3) mistrust and dehumanization. These are all closely tied to the concept of recognition, showing how the themes are configured by the social interaction between the patient and the physician and how the need for rehabilitation is shaped by this encounter. The significance of the social encounters in cancer treatment is elucidated through this analysis, and we demonstrate how the need for recognition of the complex effects of cancer on one's life is central to counter experiences of objectification and dehumanization.


Resonant scattering and mode coupling in two-dimensional textured planar waveguides.
A heuristic formalism is developed for efficiently determining the specular reflectivity spectrum of two-dimensionally textured planar waveguides. The formalism is based on a Green's function approach wherein the electric fields are assumed to vary little over the thickness of the textured part of the waveguide. Its accuracy, when the thickness of the textured region is much smaller than the wavelength of relevant radiation, is verified by comparison with a much less efficient, exact finite difference solution of Maxwell's equations. In addition to its numerical efficiency, the formalism provides an intuitive explanation of Fano-like features evident in the specular reflectivity spectrum when the incident radiation is phase matched to excite leaky electromagnetic modes attached to the waveguide. By associating various Fourier components of the scattered field with bare slab modes, the dispersion, unique polarization properties, and lifetimes of these Fano-like features are explained in terms of photonic eigenmodes that reveal the renormalization of the slab modes due to interaction with the two-dimensional grating. An application of the formalism, in the analysis of polarization-insensitive notch filters, is also discussed.


The ecological and geographic context of morphological and genetic divergence in an understorey-dwelling bird.
Advances in understanding the process of species formation require an integrated perspective that includes the evaluation of spatial, ecological and genetic components. One approach is to focus on multiple stages of divergence within the same species. Species that comprise phenotypically different populations segregated in apparently distinct habitats, in which range is presently continuous but was putatively geographically isolated provide an interesting system to study the mechanisms of population divergence. Here, we attempt to elucidate the role of ecology and geography in explaining observed morphological and genetic variation in an understorey-dwelling bird endemic to southeastern Africa, where two subspecies are recognized according to phenotype and habitat affinity. We carried out a range-wide analysis of climatic requirements, morphological and genetic variation across southeast Africa to test the hypothesis that the extent of gene flow among populations of the brown scrub-robin are influenced by their distinct climatic niches. We recovered two distinct trends depending on whether our analyses were hierarchically structured at the subspecies or at the within subspecies level. Between subspecies we found pronounced morphological differentiation associated with strong reproductive isolation (no gene flow) between populations occupying divergent climatic niches characterized by changes in the temperature of the warmest and wettest month. In contrast, within subspecies, we recovered continuous morphological variation with extensive gene flow among populations inhabiting the temperate and sub-tropical forests of southern Africa, despite divergence along the climate axis that is mainly determined by minimum temperature and precipitation of the coldest months. Our results highlight the role of niche divergence as a diversifying force that can promote reproductive isolation in vertebrates.


HIV-2 and its role in conglutinated approach towards Acquired Immunodeficiency Syndrome (AIDS) Vaccine Development.
Acquired Immunodeficiency Syndrome (AIDS) is one of the most critically acclaimed endemic diseases, caused by two lentiviruses HIV-1 and 2. HIV-2 displays intimate serological and antigenic resemblance to Simian Immunodeficiency Virus (SIV) along with less pathogenicity, lower infectivity and appreciable cross reactivity with HIV-1 antigens. The present era is confronted with the challenge to fabricate a vaccine effective against all clades of both the species of HIV. But vaccine development against HIV-1 has proven highly intricate, moreover the laborious and deficient conventional approaches has slackened the pace regarding the development of new vaccines. These concerns may be tackled with the development of HIV-2 vaccine as a natural control of HIV-1 that has been found in ancestors of HIV-2 i.e. African monkeys, mangabeys and macaques. Thereby, suggesting the notion of cross protection among HIV-2 and HIV-1. Assistance of bioinformatics along with vaccinomics strategy can bring about a quantum leap in this direction for surpassing the bottleneck in conventional approaches. These specifics together can add to our conception that HIV-2 vaccine design by in silico strategy will surely be a constructive approach for HIV-1 targeting.