The epidemiology of soil-transmitted helminths in Bihar State, India.
Soil-transmitted helminths (STHs) infect over a billion individuals worldwide. In India, 241 million children are estimated to need deworming to avert the negative consequences STH infections can have on child health and development. In February-April 2011, 17 million children in Bihar State were dewormed during a government-led school-based deworming campaign. Prior to programme implementation, a study was conducted to assess STH prevalence in the school-age population to direct the programme. The study also investigated risk factors for STH infections, including caste, literacy, and defecation and hygiene practices, in order to inform the development of complementary interventions. A cross-sectional survey was conducted among children in 20 schools in Bihar. In addition to providing stool samples for identification of STH infections, children completed a short questionnaire detailing their usual defecation and hand-hygiene practices. Risk factors for STH infections were explored. In January-February 2011, 1279 school children aged four to seventeen provided stool samples and 1157 children also completed the questionnaire. Overall, 68% of children (10-86% across schools) were infected with one or more soil-transmitted helminth species. The prevalence of ascariasis, hookworm and trichuriasis was 52%, 42% and 5% respectively. The majority of children (95%) practiced open defecation and reported most frequently cleansing hands with soil (61%). Increasing age, lack of maternal literacy and certain castes were independently associated with hookworm infection. Absence of a hand-washing station at the schools was also independently associated with A. lumbricoides infection. STH prevalence in Bihar is high, and justifies mass deworming in school-aged children. Open defecation is common-place and hands are often cleansed using soil. The findings reported here can be used to help direct messaging appropriate to mothers with low levels of literacy and emphasise the importance of water and sanitation in the control of helminths and other diseases.


Security policies and trust in ubiquitous computing.
Ubiquitous environments comprise resource-constrained mobile and wearable devices and computational elements embedded in everyday artefacts. These are connected to each other using both infrastructure-based as well as short-range ad hoc networks. Limited Internet connectivity limits the use of conventional security mechanisms such as public key infrastructures and other forms of server-centric authentication. Under these circumstances, peer-to-peer interactions are well suited for not just information interchange, but also managing security and privacy. However, practical solutions for protecting mobile devices, preserving privacy, evaluating trust and determining the reliability and accuracy of peer-provided data in such interactions are still in their infancy. Our research is directed towards providing stronger assurances of the reliability and trustworthiness of information and services, and the use of declarative policy-driven approaches to handle the open and dynamic nature of such systems. This paper provides an overview of some of the challenges and issues, and points out directions for progress.


European survey on national training activities in clinical research.
Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.


Iron status in children with autism spectrum disorder.
Children with autism spectrum disorders (ASDs) often have food selectivity and restricted diets, putting them at risk for nutritional deficiencies. Previous studies have demonstrated a high prevalence of iron deficiency (ID) in children with ASDs living in Wales, Canada, and Turkey. The objectives of this study were to determine the prevalence of ID and the adequacy of iron intake in children with ASD in the United States. Participants (age 2-11 years recruited from the Autism Treatment Network Diet and Nutrition Study) completed a 3-day diet record (n = 368) and had laboratory measures of serum ferritin (SF), complete blood count, iron, total iron binding capacity, and transferrin saturation (TS) (n = 222). Of the 222 participants with laboratory data, 18 (8%) had SF <12 µg/L and 2 (1%) had ID defined by both low SF and TS (3 children with low SF had missing TS data). One subject had iron deficiency anemia. Fewer than 2% of subjects had iron intake below the estimated average requirement. Although the determination of iron status is complex, these data do not support previous reports that children with ASD are at greater risk for ID than the general population; however, 8% percent of the sample did demonstrate low SF despite <2% of the sample demonstrating iron intake below the estimated average requirement. The prevalence of low SF may be an underestimate, because SF is an acute phase reactant and the study included no measure of inflammation.


Implementation of an all-ages mandatory helmet policy for ice skating.
Ice skaters sustain a significant number of head injuries each winter. We are the first to implement an all-ages helmet policy at a university-based Canadian arena. We report our experience from a cross-sectional observational study as well as the policy's consequences on helmet use and skating participation. Educational programming was provided prior to policy implementation. Observations of helmet use, falls and skater demographics were conducted prior to education/implementation and after policy implementation. The number of skaters observed was essentially unchanged by the policy; 361 skaters were observed pre-implementation, while 358 were observed post-implementation during the same number of observation-hours. Pre-implementation, helmet use ranged from 97% among children under 12 to 10% among adults; post-implementation use in all skaters was 99%. Falls were observed among all age groups, with preponderance among those aged 4-12. An all-ages helmet policy was successful both in achieving helmet use among all skaters and in maintaining participation rates.


Exposure to purified lignan from flaxseed (Linum usitatissimum) alters bone development in female rats.
Due to the potential oestrogenic effects of secoisolariciresinol diglycoside (SDG), the mammalian lignan precursor in flaxseed (Linum usitatissimum), we hypothesized that exposure to purified SDG during early life would have a positive effect on developing bone. This present study determined whether exposure to SDG purified from flaxseed during suckling via mother's milk or continuously to adolescence (postnatal day (PND) 50) or adulthood (PND 132) increased bone mineral content (BMC) or bone strength in female rat offspring. Offspring were exposed to basal diet (BD) or one of two doses of SDG (50S, 100S) equivalent to that in a 50 or 100 g flaxseed/kg diet during lactation only or through to PND 50 or 132. At PND 50 and 132, femurs were analysed for BMC by dual energy X-ray absorptiometry and biomechanical strength by a 3-point bending test. Compared with BD group, rats exposed to continuous 50S or 100S diet had stronger femurs at PND 50 without changes in BMC. At PND 132 there were no differences in femur strength despite the fact that continuous exposure to BD resulted in a higher BMC than rats exposed to 100S during lactation only or to 50S or 100S during lactation through to adulthood. In conclusion, female rat bone is more sensitive to the oestrogen-like action of lignans during early life when endogenous levels of sex hormones are low, but by adulthood the improved bone strength does not persist. Importantly, exposure to purified lignan does not have negative effects on bone strength.


Insight in individuals with an At Risk Mental State.
On average, people with an At Risk Mental State (ARMS) for psychosis are more willing to seek and accept clinical help than patients with psychotic disorders, suggesting that insight in this group is relatively less impaired. We compared the level and quality of insight in the ARMS and in first episode psychosis. Insight about illness was assessed in subjects with an ARMS and in patients with first episode psychosis (FEP) who were and were not help-seeking, using the Schedule for Assessment of Insight (SAI-E). Insight was impaired in ARMS subjects, but there was considerable variability in the insight displayed between subjects. Compared to FEP subjects, ARMS subjects showed greater insight, particularly with respect to Symptom Relabelling. ARMS subjects were more likely to interpret anomalous experiences as symptoms of illness, and to perceive themselves as needing treatment. Insight in people at high risk for psychosis is impaired, despite the fact that they are help-seeking. Insight varies between subjects, highlighting the need to comprehensively assess all aspects of insight in those with an ARMS. ARMS subjects are impaired in their ability to appraise anomalous experiences as symptoms of illness, but much less impaired than FEP subjects. This is consistent with cognitive models that propose that the way symptoms are appraised determines whether the individual develops a psychotic illness.


DNA-directed spatial assembly of photosynthetic light-harvesting proteins.
This manuscript describes the surface immobilization of a light-harvesting complex to prescribed locations directed by the sequence-selective recognition of duplex DNA. An engineered light-harvesting complex (RC-LH1) derived from Rhodopseudomonas (Rps.) palustris containing the zinc finger (ZF) domain zif268 was prepared. The zif268 domain directed the binding of zfRC-LH1 to target double-stranded DNA sequences both in solution and when immobilized on lithographically defined micro-patterns. Excitation energy transfer from the carotenoids to the bacteriochlorophyll pigments within zfRC-LH1 confirmed that the functional and structural integrity of the complex is retained after surface immobilization.


Modeling biochemical pathways using an artificial chemistry.
Artificial chemistries are candidates for methodologies that model and design biochemical systems. If artificial chemistries can deal with such systems in beneficial ways, they may facilitate activities in the new area of biomolecular engineering. In order to explore such possibilities, we illustrate four models of biochemical pathways described in our artificial chemistry based on string pattern matching and recombination. The modeled pathways are the replication of DNA, transcription from DNA to mRNA, translation from mRNA to protein, and the oxidation of fatty acids. The descriptions show that the present approach has good modularity and scalability that will be useful for modeling a huge network of pathways. Moreover, we give a procedure to perform reasoning in the artificial chemistry, which checks whether a specified collection of molecules can be generated in a given model, and we demonstrate that it works on a model that describes a natural biochemical pathway.


Evo-devo perspectives on cancer.
The integration of evolutionary and developmental approaches into the field of evolutionary developmental biology has opened new areas of inquiry- from understanding the evolution of development and its underlying genetic and molecular mechanisms to addressing the role of development in evolution. For the last several decades, the terms 'evolution' and 'development' have been increasingly linked to cancer, in many different frameworks and contexts. This mini-review, as part of a special issue on Evolutionary Developmental Biology, discusses the main areas in cancer research that have been addressed through the lenses of both evolutionary and developmental biology, though not always fully or explicitly integrated in an evo-devo framework. First, it briefly introduces the current views on carcinogenesis that invoke evolutionary and/or developmental perspectives. Then, it discusses the main mechanisms proposed to have specifically evolved to suppress cancer during the evolution of multicellularity. Lastly, it considers whether the evolution of multicellularity and development was shaped by the threat of cancer (a cancer-evo-devo perspective), and/or whether the evolution of developmental programs and life history traits can shape cancer resistance/risk in various lineages (an evo-devo-cancer perspective). A proper evolutionary developmental framework for cancer, both as a disease and in terms of its natural history (in the context of the evolution of multicellularity and development as well as life history traits), could bridge the currently disparate evolutionary and developmental perspectives and uncover aspects that will provide new insights for cancer prevention and treatment.


Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause.
The extent of blooming artifact may reflect the amount of paramagnetic material. We thus assessed the overestimation ratio of susceptibility vessel sign (SVS) on susceptibility-weighted imaging, defined as the extent of SVS width beyond the lumen and examined its value for predicting the stroke cause in acute ischemic stroke patients. We included consecutive acute ischemic stroke patients with proximal large artery occlusion who underwent both susceptibility-weighted imaging and time-of-flight magnetic resonance angiography within 8 hours poststroke onset. We calculated the length, width, and overestimation ratio of SVS on susceptibility-weighted imaging and then investigated their values for predicting the stroke cause, respectively. One-hundred eleven consecutive patients (72 female; mean age, 66.6±13.4 years) were enrolled, among whom 39 (35.1%) were diagnosed with cardiogenic embolism, 43 (38.7%) with large artery atherosclerosis, and 29 (26.1%) with undetermined cause. The presence, length, width, and overestimation ratio of SVS were all independently associated with the cause of cardiogenic embolism after adjusting for baseline National Institute of Health Stroke Scale and infarct volume. After excluded patients with undetermined cause, the sensitivity and specificity of overestimation ratio of SVS for cardiogenic embolism were 0.971 and 0.913; for the length of SVS, they were 0.629 and 0.739; for the width of SVS, they were 0.829 and 0.826, respectively. The overestimation ratio of SVS can predict cardiogenic embolism, with both high sensitivity and specificity, which can be helpful for the management of acute ischemic stroke patients in hyperacute stage.


Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release.
Carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its favorable antiarrhythmic benefits remain unclear. Spontaneous Ca(2+) waves, also called store overload-induced Ca(2+) release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure. Here we show that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol, combined with its beta-blocking activity, probably contributes to its favorable antiarrhythmic effect. To enable optimal titration of carvedilol's actions as a beta blocker and as a suppressor of SOICR separately, we developed a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients.


DisProt 7.0: a major update of the database of disordered proteins.
The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance (primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins.


Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors.
Controversy persists about whether certain antidepressants reduce tamoxifen's effectiveness on lowering breast cancer recurrence. We investigated whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. We examined 16 887 breast cancer survivors (TNM stages 0-II) diagnosed between 1996 and 2007 and treated with tamoxifen in two California health plans. Women were followed-up through December 31, 2009, for subsequent breast cancer. The main exposure was the percent of days of overlap when both tamoxifen and an antidepressant (paroxetine, fluoxetine, other selective serotonin reuptake inhibitors, tricyclics, and other classes) were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models with time-varying medication variables. Of the 16 887 women, half (n = 8099) used antidepressants and 2946 women developed subsequent breast cancer during the 14-year study period. We did not find a statistically significant increased risk of subsequent breast cancer in women who concurrently used paroxetine and tamoxifen. For 25%, 50%, and 75% increases in percent overlap days between paroxetine and tamoxifen, hazard ratios were 1.06 (95% CI = 0.98 to 1.14, P = .09), 1.13 (95% CI = 0.98 to 1.30, P = .09), and 1.20 (95% CI = 0.97 to 1.49, P = .09), respectively, in the first year of tamoxifen treatment but were not statistically significant. Hazard ratios decreased to 0.94 (95% CI = 0.81 to 1.10, P = .46), 0.89 (95% CI = 0.66 to 1.20, P = .46), and 0.85 (95% CI = 0.54 to 1.32, P = .46) by the fifth year (all non-statistically significantly). Absolute subsequent breast cancer rates were similar among women who used paroxetine concomitantly with tamoxifen vs tamoxifen-only users. For the other antidepressants, we again found no such associations. Using the comprehensive electronic health records of insured patients, we did not observe an increased risk of subsequent breast cancer in women who concurrently used tamoxifen and antidepressants, including paroxetine.


Determination of 2,4,6-trichloroanisole and 2,4,6-tribromoanisole in wine using microextraction in packed syringe and gas chromatography-mass spectrometry.
A selective and fast method for the quantitative determination of 2,4,6-trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine was developed. Microextraction in packed syringe (MEPS) was optimized for the extraction and preconcentration of the analytes using extremely small volume samples (0.1-1 mL). For GC-EI-MS, the limit of detection (LOD) for red and white wine was in the range 0.17-0.49 microg L(-1) for TCA and TBA. In addition to GC-EI-MS both GC-NCI-MS and GC-HRMS were used to further improve both selectivity and sensitivity. The lowest LODs were achieved using GC-HRMS in the EI mode. In red and white wine samples the LODs were between 0.22-0.75 ng L(-1) for TCA and TBA. The reproducibility and linearity for the GC-HRMS method was good, with RSD-values of 4-10% for spiked red wine samples at 1 ng L(-1) and linearity with R (2) > 0.962 over a concentration range of 1 to 100 ng L(-1).


Robo4 vaccines induce antibodies that retard tumor growth.
Tumor endothelial specific expression of Robo4 in adults identifies this plasma membrane protein as an anti-cancer target for immunotherapeutic approaches, such as vaccination. In this report, we describe how vaccination against Robo4 inhibits angiogenesis and tumor growth. To break tolerance to the auto-antigen Robo4, mice were immunised with the extracellular domain of mouse Robo4, fused to the Fc domain of human immunoglobulin within an adjuvant. Vaccinated mice show a strong antibody response to Robo4, with no objectively detectable adverse effects on health. Robo4 vaccinated mice showed impaired fibrovascular invasion and angiogenesis in a rodent sponge implantation assay, as well as a reduced growth of implanted syngeneic Lewis lung carcinoma. The anti-tumor effect of Robo4 vaccination was present in CD8 deficient mice but absent in B cell or IgG1 knockout mice, suggesting antibody dependent cell mediated cytotoxicity as the anti-vascular/anti-tumor mechanism. Finally, we show that an adjuvant free soluble Robo4-carrier conjugate can retard tumor growth in carrier primed mice. These results point to appropriate Robo4 conjugates as potential anti-angiogenic vaccines for cancer patients.


Do the pre-service education programmes for midwives in India prepare confident 'registered midwives'? A survey from India.
Objective The graduates of the diploma and degree programmes of nursing and midwifery in India are considered skilled birth attendants (SBAs). This paper aimed to assess the confidence of final-year students from pre-service education programmes (diploma and bachelor's) in selected midwifery skills from the list of midwifery competencies of the International Confederation of Midwives (ICM). Design A cross-sectional survey was conducted in Gujarat, India, involving 633 final-year students from 25 educational institutions (private or government), randomly selected, stratified by the type of programme (diploma and bachelor's). Students assessed their confidence on a four-point scale, in four midwifery competency domains - antepartum, intrapartum, postpartum, and newborn care. Explorative factor analysis was used to reduce skill statements into separate subscales for each domain. Results Overall, 25-40% of students scored above the 75th percentile and 38-50% below the 50th percentile of confidence in all subscales for antepartum, intrapartum, postpartum, and newborn care. The majority had not attended the required number of births prescribed by the Indian Nursing Council. Conclusions The pre-service education offered in the diploma and bachelor's programmes in Gujarat does not prepare confident SBAs, as measured on selected midwifery competencies of the ICM. One of the underlying reasons was less clinical experience during their education. The duration, content, and pedagogy of midwifery education within the integrated programmes need to be reviewed.


Biodistribution and metabolism studies of lipid nanoparticle-formulated internally [3H]-labeled siRNA in mice.
Absorption, distribution, metabolism, and excretion properties of a small interfering RNA (siRNA) formulated in a lipid nanoparticle (LNP) vehicle were determined in male CD-1 mice following a single intravenous administration of LNP-formulated [(3)H]-SSB siRNA, at a target dose of 2.5 mg/kg. Tissue distribution of the [(3)H]-SSB siRNA was determined using quantitative whole-body autoradiography, and the biostability was determined by both liquid chromatography mass spectrometry (LC-MS) with radiodetection and reverse-transcriptase polymerase chain reaction techniques. Furthermore, the pharmacokinetics and distribution of the cationic lipid (one of the main excipients of the LNP vehicle) were investigated by LC-MS and matrix-assisted laser desorption ionization mass spectrometry imaging techniques, respectively. Following i.v. administration of [(3)H]-SSB siRNA in the LNP vehicle, the concentration of parent guide strand could be determined up to 168 hours p.d. (post dose), which was ascribed to the use of the vehicle. This was significantly longer than what was observed after i.v. administration of the unformulated [(3)H]-SSB siRNA, where no intact parent guide strand could be observed 5 minutes post dosing. The disposition of the siRNA was determined by the pharmacokinetics of the formulated LNP vehicle itself. In this study, the radioactivity was widely distributed throughout the body, and the total radioactivity concentration was determined in selected tissues. The highest concentrations of radioactivity were found in the spleen, liver, esophagus, stomach, adrenal, and seminal vesicle wall. In conclusion, the LNP vehicle was found to drive the kinetics and biodistribution of the SSB siRNA. The renal clearance was significantly reduced and its exposure in plasma significantly increased compared with the unformulated [(3)H]-SSB siRNA.


Pathology of the rectal wall in solitary rectal ulcer syndrome and complete rectal prolapse.
The aetiology and pathology of rectal prolapse and solitary rectal ulcer are poorly understood. To examine the full thickness rectal wall in these two conditions. The pathological abnormalities in the surgically resected rectal wall were studied from nine patients with solitary rectal ulcer syndrome, 11 complete rectal prolapse, and nine cancer controls. Routine haematoxylin and eosin and Van Gieson staining for collagen were performed. The rectal wall from solitary rectal ulcer syndrome specimens was thickened compared with complete rectal prolapse and controls. The major difference was in the muscularis propria (2.2 v 1.1 v 1.2 mm, medians, p < 0.005) and particularly the inner circular muscular layer, and to a lesser extent the submucosal and outer longitudinal muscular layers. Some solitary rectal ulcer syndrome specimens showed unique features such as decussation of the two muscular layers (four of nine), nodular induration of inner circular layer (four of nine) and grouping of outer longitudinal layer into bundles (three of nine); these were not seen in complete rectal prolapse or control specimens. These features, which resemble the features of high pressure sphincter tissue, may be of aetiological importance, and suggest a different pathogenesis for these two disorders. Excess collagen was seen in both disorders, was more severe in solitary rectal ulcer syndrome specimens, and probably reflects a response to repeated trauma.


Browsing zoomable treemaps: structure-aware multi-scale navigation techniques.
Treemaps provide an interesting solution for representing hierarchical data. However, most studies have mainly focused on layout algorithms and paid limited attention to the interaction with treemaps. This makes it difficult to explore large data sets and to get access to details, especially to those related to the leaves of the trees. We propose the notion of zoomable treemaps (ZTMs), an hybridization between treemaps and zoomable user interfaces that facilitates the navigation in large hierarchical data sets. By providing a consistent set of interaction techniques, ZTMs make it possible for users to browse through very large data sets (e.g., 700,000 nodes dispatched amongst 13 levels). These techniques use the structure of the displayed data to guide the interaction and provide a way to improve interactive navigation in treemaps.


An investigation of the association between grip strength and hip and knee joint moments in older adults.
Grip strength is a predictor of health outcomes but with differing rates of age-related decline in muscle strength, it is unclear whether handgrip is a reliable indicator of lower limb moments. This study investigated the relationship between grip strength and lower extremity moments in community-dwelling older adults. Eighty-two healthy volunteers aged 60-82 years (mean age 73.2 years) performed maximal voluntary contractions of knee and hip extensors and flexors at three positions and at neutral position for hip abductors and adductors using a custom-built dynamometer. Grip strength was measured using an electronic Jamar dynamometer. The relative reduction in muscle strength of 80s age category compared to 60-year-olds ranged from 14% for grip strength to 27% for hip abductors. Peak torque of flexors and extensors of the knee and hip joints were significantly correlated with grip strength and Pearson's correlation coefficients ranged from 0.56 to 0.78 with the highest correlations observed between knee moments and grip strength. "Good" correlation was found but only 31-60% of the variation in grip strength could be related to changes in joint torques. Hence the assumption that grip strength is an indicator of strength in the lower limb would seem unjustified in the healthy older adult.


Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals: A Randomized Controlled Trial.
To investigate the effects of 10 weeks of progressive vigorous-intensity interval training as a single intervention on body composition among 70-year-old individuals with central obesity. Randomized controlled trial (ClinicalTrials.gov registration No. NCT03450655). Community-dwelling 70-year-old men and women living in the Umeå municipality in Sweden. Seventy-seven 70-year-old men and women with central obesity (greater than 1 kg visceral adipose tissue [VAT] for women and greater than 2 kg VAT for men). Participants allocated to the intervention group were offered a 10-week progressive concurrent exercise program performed three times per week. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. The primary outcome was changes in VAT, and secondary outcomes included changes in total fat mass (FM), total lean body mass (LBM), and body mass index. Comparing the groups, there were no significant differences in decrease of VAT mass (P = .10), although the intervention group significantly decreased FM by 716 g (P = .01) and gained LBM by 508 g (P = .03), compared to the control group. Furthermore, the effects of the training were significantly greater in the male subcohort (P < .05 for interaction), with positive effects also on VAT and FM, where men in the intervention group decreased VAT by 175 g (P < .05) and FM by 1364 g (P = .004), compared to the male controls. The present trial demonstrates that 10 weeks of progressive vigorous interval training is sufficient to significantly decrease FM in older adults with central obesity, with positive effects also on LBM. J Am Geriatr Soc 67:1625-1631, 2019.


Contribution of continuing gas exchange to phase III exhaled PCO2 and PO2 profiles.
Changes in PCO2 and PO2 during expiration have been ascribed to simultaneous gas exchange, but other factors such as ventilation-perfusion inhomogeneity in combination with sequential emptying may also contribute. An experimental and model approach was used to study the relationship between gas exchange and changes in expired PCO2 and PO2 in anesthetized dogs during prolonged high tidal volume expirations. Changes in PCO2 and PO2 were quantified by taking the area bounded by the sloping exhalation curve and a line drawn horizontally from a point where the Fowler dead space plus 250 ml had been expired. This procedure is similar to using the slope of the exhalation curve but it circumvents problems caused by nonlinearity of the PCO2 and PO2 curves. The gas exchange components of the CO2 and O2 areas were calculated using a single-alveolus lung model whose input parameters were measured in connection with each prolonged expiration. The relationship between changes in experimental CO2 areas caused by sudden reductions in mixed venous PCO2 (produced by right atrial infusions of NaOH) and those calculated by the model was also studied. In seven dogs, calculated CO2 and O2 areas were 13% higher and 25% lower than the respective experimental areas, but interindividual variations were large. Changes in experimental CO2 areas caused by step changes in mixed venous PCO2 were almost identical to changes in the calculated areas. We conclude that the changes in PCO2 and PO2 during expiration cannot be explained solely by gas exchange. However, the single-alveolus lung model accurately predicts changes in the CO2 exhalation curve caused by alterations in the alveolar CO2 flow.


Low Cancer Screening Rates among Japanese People with Schizophrenia: A Cross-Sectional Study.
Health care disparities among people with schizophrenia is a global concern. Our previous study revealed cancer screening rates in Japanese people with schizophrenia lower than rates of approximately 40% of the general population. However, that study was based on self-reports, which can be inaccurate, and rates did not differentiate the types of cancer screening provider (i.e., municipal screening, collective opportunistic screening, and individual opportunistic screening). This study aimed to investigate records-based cancer screening rates, focusing on participation rates of people with schizophrenia who are subject to municipal cancer screening programs. We conducted a cross-sectional study at a psychiatric hospital outpatient clinic from September to November 2016. We randomly extracted 420 potential participants from among 680 eligible patients and asked them to participate. We then selected subgroups of participants living in Okayama city who were enrolled in the National Health Insurance or Public Assistance systems and were subject to colorectal, gastric, lung, breast, or cervical cancer screening provided by Okayama city (n = 97, 96, 97, 42, and 64, respectively). Participation in cancer screenings was assessed based on local government records. Municipal cancer screening rates were as follows: 13.4% (95% confidence interval: 6.6%-20.2%) for colorectal, 7.3% (2.1%-12.5%) for gastric, 16.5% (9.1%-23.9%) for lung, 21.4% (9.0%-33.8%) for breast, and 14.1% (5.6%-22.6%) for cervical cancers. The findings demonstrated extremely low cancer screening rates among people with schizophrenia subject to municipal cancer screenings in Japan. A strategy to promote municipal cancer screening for people with schizophrenia is needed.


Electrocardiogram findings in emergency department patients with syncope.
To determine the sensitivity and specificity of the San Francisco Syncope Rule (SFSR) electrocardiogram (ECG) criteria for determining cardiac outcomes and to define the specific ECG findings that are the most important in patients with syncope. A consecutive cohort of emergency department (ED) patients with syncope or near syncope was considered. The treating emergency physicians assessed 50 predictor variables, including an ECG and rhythm assessment. For the ECG assessment, the physicians were asked to categorize the ECG as normal or abnormal based on any changes that were old or new. They also did a separate rhythm assessment and could use any of the ECGs or available monitoring strips, including prehospital strips, when making this assessment. All patients were followed up to determine a broad composite study outcome. The final ECG criterion for the SFSR was any nonsinus rhythm or new ECG changes. In this specific study, the initial assessments in the database were used to determine only cardiac-related outcomes (arrhythmia, myocardial infarction, structural, sudden death) based on set criteria, and the authors determined the sensitivity and specificity of the ECG criteria for cardiac outcomes only. All ECGs classified as "abnormal" by the study criteria were compared to the official cardiology reading to determine specific findings on the ECG. Univariate and multivariate analysis were used to determine important specific ECG and rhythm findings. A total of 684 consecutive patients were considered, with 218 having positive ECG criteria and 42 (6%) having important cardiac outcomes. ECG criteria predicted 36 of 42 patients with cardiac outcomes, with a sensitivity of 86% (95% confidence interval [CI] = 71% to 94%), a specificity of 70% (95% CI = 66% to 74%), and a negative predictive value of 99% (95% CI = 97% to 99%). Regarding specific ECG findings, any nonsinus rhythm from any source and any left bundle conduction problem (i.e., any left bundle branch block, left anterior fascicular block, left posterior fascicular block, or QRS widening) were 2.5 and 3.5 times more likely associated with significant cardiac outcomes. The ECG criteria from the SFSR are relatively simple, and if used correctly can help predict which patients are at risk of cardiac outcomes. Furthermore, any left bundle branch block conduction problems or any nonsinus rhythms found during the ED stay should be especially concerning for physicians caring for patients presenting with syncope.


Storm impacts on phytoplankton community dynamics in lakes.
In many regions across the globe, extreme weather events such as storms have increased in frequency, intensity, and duration due to climate change. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. High winds and precipitation associated with storms can affect lakes via short-term runoff events from watersheds and physical mixing of the water column. In addition, lakes connected to rivers and streams will also experience flushing due to high flow rates. Although we have a well-developed understanding of how wind and precipitation events can alter lake physical processes and some aspects of biogeochemical cycling, our mechanistic understanding of the emergent responses of phytoplankton communities is poor. Here we provide a comprehensive synthesis that identifies how storms interact with lake and watershed attributes and their antecedent conditions to generate changes in lake physical and chemical environments. Such changes can restructure phytoplankton communities and their dynamics, as well as result in altered ecological function (e.g., carbon, nutrient and energy cycling) in the short- and long-term. We summarize the current understanding of storm-induced phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions across a gradient of lake types and environmental conditions.


Glutamate and aspartate immunoreactivity in hypothalamic presynaptic axons.
Within the hypothalamus, a large number of neuroactive substances are found, many first detected in this part of the brain. Excitatory amino acids, recognized as important transmitters in other parts of the brain, have received little attention here. To study glutamate immunoreactivity at the ultrastructural level in the hypothalamus, postembedding colloidal gold or silver-intensified gold was used. Antisera raised against glutamate conjugated with glutaraldehyde to keyhole limpet hemocyanin were specific for glutamate, tested with a battery of tests including immunodot blot, ELISA assays. Western blot, and Sepharose epoxy-conjugated amino acids. Antisera did not cross-react with other amino acids and related compounds, with proteins containing glutamate, or with polyglutamate. A population of presynaptic boutons in the suprachiasmatic, arcuate, ventromedial, supraoptic, and parvocellular and magnocellular paraventricular nuclei showed strong immunoreactivity for glutamate. Highly labeled presynaptic axons generally made asymmetrical Gray type 1 synaptic contacts with dendrites or cell bodies and had up to eight times more immunogold particles per unit area than postsynaptic dendrites. Axon terminals exhibiting strong glutamate immunoreactivity had large numbers of round, clear vesicles adjacent to the synaptic specialization together with a few larger, dense-core vesicles. The largest number of gold particles over axons were located in regions containing the small clear vesicles. Axons in general had about three times more gold particles over them than did the postsynaptic dendrites. Staining of single boutons in adjacent serial ultrathin sections with glutamate or GABA antisera showed that non-GABAergic terminals had a higher level of glutamate staining than did axons immunoreactive for GABA. In control experiments, immunostaining with glutamate antiserum could be blocked by solid-phase absorption of the antiserum with glutamate conjugated with glutaraldehyde to proteins. Aspartate was also detected with immunocytochemistry in some presynaptic boutons in the medial hypothalamus. To compare the response of neurons to aspartate and glutamate, calcium-imaging dyes were used in combination with digital video microscopy. Whereas almost all neurons showed a rise in intracellular Ca2+ in response to glutamate, many but not all of the same cells also showed a Ca2+ rise of smaller magnitude in response to aspartate. These ultrastructural immunocytochemical data, taken in conjunction with biochemical and electrophysiological experiments, suggest that glutamate, and to a lesser extent aspartate, may play an important neurotransmitter role in a wide variety of hypothalamic circuits.


Investigating determinants of out-of-pocket spending and strategies for coping with payments for healthcare in southeast Nigeria.
Out-of-pocket spending (OOPS) is the major payment strategy for healthcare in Nigeria. Hence, the paper assessed the determinants socio-economic status (SES) of OOPS and strategies for coping with payments for healthcare in urban, semi-urban and rural areas of southeast Nigeria. This paper provides information that would be required to improve financial accessibility and equity in financing within the public health care system. The study areas were three rural and three urban areas from Ebonyi and Enugu states in South-east Nigeria. Cross-sectional survey using interviewer-administered questionnaires to randomly selected householders was the study tool. A socio-economic status (SES) index that was developed using principal components analysis was used to examine levels of inequity in OOPS and regression analysis was used to examine the determinants of use of OOPS. All the SES groups equally sought healthcare when they needed to. However, the poorest households were most likely to use low level and informal providers such as traditional healers, whilst the least poor households were more likely to use the services of higher level and formal providers such as health centres and hospitals. The better-off SES more than worse-off SES groups used OOPS to pay for healthcare. The use of own money was the commonest payment-coping mechanism in the three communities. The sales of movable household assets or land were not commonly used as payment-coping mechanisms. Decreasing SES was associated with increased sale of household assets to cope with payment for healthcare in one of the communities. Fee exemptions and subsidies were almost non-existent as coping mechanisms in this study There is the need to reduce OOPS and channel and improve equity in healthcare financing by designing and implementing payment strategies that will assure financial risk protection of the poor such pre-payment mechanisms with government paying for the poor.


Genetic tool development in marine protists: emerging model organisms for experimental cell biology.
Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.


Mechanical circulatory support devices for acute heart failure syndromes: considerations for clinical trial design.
Mechanical circulatory support (MCS) devices are a guideline-recommended treatment option for a small subset of advanced heart failure patients. MCS has the potential to become more prominent in the management of Acute Heart Failure Syndromes (AHFS) as device technology advances and as clinical trials consistently discover neutral or harmful effects with pharmacologic therapies hypothesized to be beneficial in this population. While it is now possible to identify AHFS patients who are at high risk of death, the therapeutic options available to improve their long-term outcomes are limited. MCS therapy in this population offers a "bridge to recovery" strategy; these patients may have viable myocardium that responds favorably to the influence of MCS on neurohormones, cytokines, and/or reverse remodeling. Patients at high risk for mortality who have a substantial likelihood of benefiting from MCS can be easily identified using standard clinical criteria developed from large observational databases. MCS technology is rapidly evolving, and risks related to implantation are declining. It is evident that rigorous clinical trial testing of the potential risks, benefits, and economic implications of MCS in patients with AHFS will need to be conducted before the "routine" application of this aggressive therapy. This paper examines the rationale for conducting trials of MCS devices in patients with AHFS, and it explores considerations for patient selection and appropriate endpoints. This manuscript was generated from discussions on this issue during the third international meeting of the International Working Group on AHFS held in Washington, DC, April 8-9, 2006.


Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen.
The prolyl hydroxylase domain proteins (PHDs) catalyse the post-translational hydroxylation of the hypoxia-inducible factor (HIF), a modification that regulates the hypoxic response in humans. The PHDs are Fe(II)/2-oxoglutarate (2OG) oxygenases; their catalysis is proposed to provide a link between cellular HIF levels and changes in O2 availability. Transient kinetic studies have shown that purified PHD2 reacts slowly with O2 compared with some other studied 2OG oxygenases, a property which may be related to its hypoxia-sensing role. PHD2 forms a stable complex with Fe(II) and 2OG; crystallographic and kinetic analyses indicate that an Fe(II)-co-ordinated water molecule, which must be displaced before O2 binding, is relatively stable in the active site of PHD2. We used active site substitutions to investigate whether these properties are related to the slow reaction of PHD2 with O2. While disruption of 2OG binding in a R383K variant did not accelerate O2 activation, we found that substitution of the Fe(II)-binding aspartate for a glutamate residue (D315E) manifested significantly reduced Fe(II) binding, yet maintained catalytic activity with a 5-fold faster reaction with O2. The results inform on how the precise active site environment of oxygenases can affect rates of O2 activation and provide insights into limiting steps in PHD catalysis.


Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases.
Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment. We retrospectively reviewed all 4 cases (aged 38-77 years) of transtibial amputations managed with osseointegration and TKR in 2012-2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1-3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test. There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29-52 and a 6-minute walk test improvement range of 37-84 meters. It is possible to combine TKR with osseointegrated implants.


Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis.
To determine the diagnostic accuracy of two "spot urine" tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Systematic review and meta-analysis. Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). The maternal "spot urine" estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome.


Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration.
Axonal regeneration relies on the expression of regenerative associated genes within a coordinated transcriptional programme, which is finely tuned as a result of the activation of several regenerative signalling pathways. In mammals, this chain of events occurs in neurons following peripheral axonal injury, however it fails upon axonal injury in the central nervous system, such as in the spinal cord and the brain. Accumulating evidence has been suggesting that epigenetic control is a key factor to initiate and sustain the regenerative transcriptional response and that it might contribute to regenerative success versus failure. This review will discuss experimental evidence so far showing a role for epigenetic regulation in models of peripheral and central nervous system axonal injury. It will also propose future directions to fill key knowledge gaps and to test whether epigenetic control might indeed discriminate between regenerative success and failure.


In-Depth Investigation into the Transient Humidity Response at the Body-Seat Interface on Initial Contact Using a Dual Temperature and Humidity Sensor.
Relative humidity (RH) at the body-seat interface is considered an important factor in both sitting comfort and generation of health concerns such as skin lesions. Technical difficulties appear to have limited research aimed at the detailed and simultaneous exploration of RH and temperature changes at the body-seat interface; using RH sensors without the capability to record temperature where RH is recorded. To explore the causes of a spike in RH consistently produced on first contact between body and seat surface, we report data from the first use of dual temperature and RH (HTU21D) sensors in this interface. Following evaluation of sensor performance, the effect of local thermal changes on RH was investigated. The expected strong negative correlation between temperature and RH (R² = -0.94) supported the importance of considering both parameters when studying impact of sitting on skin health. The influence of sensor movement speed (higher velocity approach: 0.32 cm/s ± 0.01 cm/s; lower velocity approach: 0.17 cm/s ± 0.01 cm/s) into a static RH region associated with a higher local temperature were compared with data gathered by altering the rate of a person sitting. In all cases, the faster sitting down (or equivalent) generated larger RH outcomes: e.g., in human sitting 53.7% ± 3.3% RH (left mid-thigh), 56.4% ± 5.1% RH (right mid-thigh) and 53.2% ± 2.7% RH (Coccyx). Differences in size of RH change were seen across the measurement locations used to study the body-seat interface. The initial sitting contact induces a transient RH response (duration ≤ 40 s) that does not accurately reflect the microenvironment at the body-seat interface. It is likely that any movement during sitting would result in similar artefact formation. As a result, caution should be taken when investigating RH performance at any enclosed interface when the surfaces may have different temperatures and movement may occur.


A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women.
To assess the joint influence of inflammatory biomarkers on the risk of incident atrial fibrillation (AF) in women. We performed a prospective cohort study among women participating in the Women's Health Study. All women were free of AF at study entry and provided a baseline blood sample assayed for high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and fibrinogen. To evaluate the joint effect of these three biomarkers, an inflammation score was created that ranged from 0 to 3 and reflected the number of biomarkers in the highest tertile per individual. During a median follow-up of 14.4 years, 747 of 24,734 women (3.0%) experienced a first AF event. Assessed individually, all three biomarkers were associated with incident AF, even after adjustment for traditional risk factors. When combined into an inflammation score, a strong and independent relationship between inflammation and incident AF emerged. Across increasing inflammation score categories, there were 1.66, 2.22, 2.73, and 3.25 AF events per 1000 person-years of follow-up. The corresponding hazard ratios (95% confidence intervals) across inflammation score categories were 1.0, 1.22 (1.00-1.49), 1.32 (1.06-1.65), and 1.59 (1.22-2.06) (P for linear trend 0.0006) after multivariable adjustment. In this large-scale prospective study among women without a history of cardiovascular disease, markers of systemic inflammation were significantly related to AF even after controlling for traditional risk factors.


End-of-career practice patterns of primary care physicians in Ontario.
To characterize the process of end-of-career attrition among primary care physicians. Longitudinal, open cohort, population-based study of primary care physicians using health administrative data from ICES.Setting Ontario. All family physicians providing comprehensive care between 1992 and 2013. Changes in workload and scopes of practice over time. The cohort included 15 552 family physicians who provided comprehensive care at some point during the study period. Physicians reduced workloads and narrowed scopes of practice in advance of full retirement at an average age of 70.5 (95% CI 70.1 to 70.8) years. Female physicians provided fewer clinical services than male physicians did and retired 5 years earlier. Canadian medical graduates provided fewer clinical services and retired 2 years earlier than international medical graduates did. Up to 60% of physicians stopped providing comprehensive primary care before retirement, continuing with other clinical activities, at reduced workloads, for an average of 3 years before retiring fully. End-of-career practice patterns are characterized by gradual, modest changes in the provision of services rather than abrupt declines, and the retirement process unfolds differently for different physicians. This study highlights the importance of considering physician workload, scope of practice, and demographic factors for more accurate prediction of physician retirement trends and effective work force planning.


Brilliantia kiribatiensis, a new genus and species of Cladophorales (Chlorophyta) from the remote coral reefs of the Southern Line Islands, Pacific Ocean.
The marine green alga Brilliantia kiribatiensis gen. et sp. nov. is described from samples collected from the coral reefs of the Southern Line Islands, Republic of Kiribati, Pacific Ocean. Phylogenetic analysis of sequences of the large- and small-subunit rDNA and the rDNA internal transcribed spacer region revealed that Brilliantia is a member of the Boodleaceae (Cladophorales), containing the genera Apjohnia, Boodlea, Cladophoropsis, Chamaedoris, Phyllodictyon, and Struvea. Within this clade it formed a distinct lineage, sister to Struvea elegans, but more distantly related to the bona fide Struvea species (including the type S. plumosa). Brilliantia differs from the other genera by having a very simple architecture forming upright, unbranched, single-celled filaments attached to the substratum by a rhizoidal mat. Cell division occurs by segregative cell division only at the onset of reproduction. Based on current sample collection, B. kiribatiensis seems to be largely restricted to the Southern Line Islands, although it was also observed on neighboring islands, including Orona Atoll in the Phoenix Islands of Kiribati, and the Rangiroa and Takapoto Atolls in the Tuamotus of French Polynesia. This discovery highlights the likeliness that there is still much biodiversity yet to be discovered from these remote and pristine reefs of the central Pacific.


Affordable Care Act and cancer stage at diagnosis in an underserved population.
The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.


Early coagulopathy in patients with ruptured abdominal aortic aneurysm.
Ruptured abdominal aortic aneurysm (AAA) is associated with a high mortality despite surgical management. Earlier reports indicate that a major cause of immediate intraoperative death in patients with ruptured AAA is related to hemorrhage due to coagulopathy. Acidosis is, besides hypothermia and hemodilution, a possible cause of coagulopathy. The aim of the present study was to investigate the incidence of coagulopathy and acidosis preoperatively in patients with ruptured AAA in relation to the clinical outcome with special regard to the influence of shock. For this purpose, 95 consecutive patients who underwent surgery for AAA (43 ruptured with shock, 12 ruptured without shock, and 40 nonruptured) were included. Coagulopathy was defined as prothrombin time (international normalized ratio [INR]) ≥1.5 and acidosis was defined as base deficit ≥6 mmol/L. Mortality and postoperative complications were recorded. The present study shows a state of acidosis at the start of surgery in 30 of 55 patients with ruptured AAA. However, only in 7 of 55 patients with ruptured AAA a state of preoperative coagulopathy was demonstrated. Furthermore, in our patients with shock due to ruptured AAA only 2 of 12 deaths were due to coagulopathy and bleeding. Indeed, our results show a relatively high incidence of thrombosis-related causes of death in patients with ruptured AAA, indicating a relation to an activated coagulation in these patients. These findings indicate that modern emergency management of ruptured AAA has improved in the attempt to prevent fatal coagulopathy.


tRNA aminoacylation by arginyl-tRNA synthetase: induced conformations during substrates binding.
The 2.2 A crystal structure of a ternary complex formed by yeast arginyl-tRNA synthetase and its cognate tRNA(Arg) in the presence of the L-arginine substrate highlights new atomic features used for specific substrate recognition. This first example of an active complex formed by a class Ia aminoacyl-tRNA synthetase and its natural cognate tRNA illustrates additional strategies used for specific tRNA selection. The enzyme specifically recognizes the D-loop and the anticodon of the tRNA, and the mutually induced fit produces a conformation of the anticodon loop never seen before. Moreover, the anticodon binding triggers conformational changes in the catalytic center of the protein. The comparison with the 2.9 A structure of a binary complex formed by yeast arginyl-tRNA synthetase and tRNA(Arg) reveals that L-arginine binding controls the correct positioning of the CCA end of the tRNA(Arg). Important structural changes induced by substrate binding are observed in the enzyme. Several key residues of the active site play multiple roles in the catalytic pathway and thus highlight the structural dynamics of the aminoacylation reaction.


ROS perception in Arabidopsis thaliana: the ozone-induced calcium response.
Ozone is responsible for more crop losses than any other air pollutant. The changes in gene expression, which occur in plants in response to ozone, have been well characterized, yet little is known about how ozone is perceived or the signal transduction steps that follow. The earliest characterized response to ozone is an elevation in cytosolic-free calcium, which takes place within seconds of exposure. In this study, the calcium response to ozone was investigated in Arabidopsis thaliana seedlings using a variety of fumigation protocols. Ozone elicited distinct calcium responses in the aerial tissue and roots of seedlings. The calcium response in the cotyledons and leaves was biphasic and sensitive to the rate at which the ozone concentration increased. The response in the root was monophasic and insensitive to the rate of increase in ozone concentration. Experiments utilizing inhibitors of antioxidant metabolism demonstrated that the magnitude of the first peak in calcium in the aerial tissues was dependent upon the redox status of the plant. Seedlings were shown to be able to distinguish between ozone and hydrogen peroxide, producing a calcium signal in response to one of these reactive oxygen species (ROS) when they had become refractory to the other. Pre-treatment with ozone altered the calcium response to hydrogen peroxide and vice versa, indicating that the calcium response to a given ROS may reflect the stress history of the plant. These data suggest ROS signalling is more sophisticated than previously realized and raise questions over current models of ozone perception.


What's Past is Prologue: A Scoping Review of Recent Public Health and Global Health Informatics Literature.
To categorize and describe the public health informatics (PHI) and global health informatics (GHI) literature between 2012 and 2014. We conducted a semi-systematic review of articles published between January 2012 and September 2014 where information and communications technologies (ICT) was a primary subject of the study or a main component of the study methodology. Additional inclusion and exclusion criteria were used to filter PHI and GHI articles from the larger biomedical informatics domain. Articles were identified using MEDLINE as well as personal bibliographies from members of the American Medical Informatics Association PHI and GHI working groups. A total of 85 PHI articles and 282 GHI articles were identified. While systems in PHI continue to support surveillance activities, we identified a shift towards support for prevention, environmental health, and public health care services. Furthermore, articles from the U.S. reveal a shift towards PHI applications at state and local levels. GHI articles focused on telemedicine, mHealth and eHealth applications. The development of adequate infrastructure to support ICT remains a challenge, although we identified a small but growing set of articles that measure the impact of ICT on clinical outcomes. There is evidence of growth with respect to both implementation of information systems within the public health enterprise as well as a widening of scope within each informatics discipline. Yet the articles also illuminate the need for more primary research studies on what works and what does not as both searches yielded small numbers of primary, empirical articles. While the body of knowledge around PHI and GHI continues to mature, additional studies of higher quality are needed to generate the robust evidence base needed to support continued investment in ICT by governmental health agencies.


The optoretinogram reveals the primary steps of phototransduction in the living human eye.
Photoreceptors initiate vision by converting photons to electrical activity. The onset of the phototransduction cascade is marked by the isomerization of photopigments upon light capture. We revealed that the onset of phototransduction is accompanied by a rapid (<5 ms), nanometer-scale electromechanical deformation in individual human cone photoreceptors. Characterizing this biophysical phenomenon associated with phototransduction in vivo was enabled by high-speed phase-resolved optical coherence tomography in a line-field configuration that allowed sufficient spatiotemporal resolution to visualize the nanometer/millisecond-scale light-induced shape change in photoreceptors. The deformation was explained as the optical manifestation of electrical activity, caused due to rapid charge displacement following isomerization, resulting in changes of electrical potential and surface tension within the photoreceptor disc membranes. These all-optical recordings of light-induced activity in the human retina constitute an optoretinogram and hold remarkable potential to reveal the biophysical correlates of neural activity in health and disease.


Sending mixed messages for cell population control.
Cells often receive signals to proliferate, but how population density is controlled is unclear. Hart et al. now show that a single secreted molecule that instructs both proliferation and death in T cells establishes a bistable response: the population is driven to either extinction or to a homeostatically defined density.


The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results.
Suicide is a major health concern. Effective acute interventions are lacking. Recent studies have suggested an acute decrease of suicidal ideations following repetitive Transcranial Magnetic Stimulation (rTMS). However, placebo effects could not be excluded. We aimed to evaluate the acute effect of accelerated intermittent theta burst stimulation (TBS) on suicide risk in depression. In 12 suicidal therapy-resistant depressed patients accelerated intermittent TBS was delivered on the left dorsolateral prefrontal cortex in a randomized, sham-controlled cross-over fashion. Patients received 20 sessions spread over 4 days. The change in severity of suicidal ideation was measured by the Beck Scale of Suicidal Ideation (SSI) before and after treatment. We found a significant decrease of SSI score over time; unrelated to active or sham stimulation. Furthermore, the attenuation of suicidal thinking was not merely related to depression severity changes caused by TBS. Accelerated TBS treatment in depressed suicidal patients was found to be safe and well tolerated and may have the potential to acutely decrease suicidal ideations. However, the efficacy compared to sham has not yet been proven and further sham-controlled research including longer follow-up is needed to substantiate these preliminary findings.


Medical examination of sexually abused children: medico-legal value.
The Department of Forensic Medicine (forensic pathology and clinical forensic medicine), Aarhus, Jutland, Denmark, performs examinations of children suspected to have been sexually abused when reported to and requested by the police in Jutland, Denmark. Jutland covers an area of 210,000 km2 with about 300,000 inhabitants in Aarhus. A colposcope initially equipped with an Olympus camera, but now with a video camera attached has been used since 1994. Since 1994 the department has performed more than 100 examinations of children suspected of having been sexually abused. A preliminary study was taken to evaluate all cases from 1995 including the legal outcome. The material included 34 cases with three boys, mean age 11 years, and 31 girls, mean age 8 years, at the time of the examination. The sexual abuse events were fondling including penetration of the vagina, vaginal (14), anal (7), and oral (5) intercourse as well as cunnilingus and nontouching abuses. The medical examination was most often performed more than a week after the abuse. The examination revealed normal findings in 23 cases, nonspecific findings including erytherma in 13 cases, and in only one child was a traumatic lesion with rupture of the hymen seen. The perpetrators were above 25 years of ane and were family members or someone known to the child. Nine perpetrators were convicted at court, of whom three admitted having abused the child. A medical examination in cases of sexual child abuse seldom provides a legal proof of sexual abuse. The most important is the story told by the child. Therefore, the examination is a supplement which may support or remain neutral to the story told by the child.


A Standardized Parameter-Free Algorithm for Combined Intravoxel Incoherent Motion and Diffusion Kurtosis Analysis of Diffusion Imaging Data.
The aims of this study were to implement and systematically evaluate the performance of a new parameter-free segmented algorithm for analysis of diffusion imaging data using a combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) model of spin diffusion in comparison with the simpler intravoxel incoherent motion (IVIM) model. A multistep algorithm was implemented intended to separate diffusion kurtosis from IVIM effects in multi-b-value diffusion measurements using an adaptive b-value threshold technique. For each possible b-value threshold (separating diffusion and perfusion effects), diffusion kurtosis analysis of high b-values is followed by IVIM analysis keeping kurtosis parameters fixed. The b-value threshold with smallest Akaike information criterion is chosen as best model solution. The algorithm was tested in diffusion data sets of the upper abdomen from 8 healthy volunteers with 16 different b-values and compared with a standard multistep IVIM analysis. The proposed algorithm could successfully be applied to all data sets and provided a significantly better fit of the observed signal decay in all assessed organs (all P < 0.03). Using the proposed IVIM-DKI model of diffusion instead of an IVIM model had a systematic impact on the resulting IVIM parameters: The pure diffusion coefficient and the pseudodiffusion coefficient were significantly increased (P < 0.03 in all assessed organs), accompanied by a decrease in the perfusion fraction in liver, pancreas, renal cortex, and skeletal muscle (all P < 0.02). Optimal b-value thresholds separating diffusion from perfusion effects had a tendency to lower values when the IVIM-DKI model was used. The proposed algorithm provides a new approach for separation of IVIM and kurtosis effects of diffusion data without organ-specific adaptation.


A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression.
A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.


Reaction of Sorghum Lines Genetically Modified for Reduced Lignin Content to Infection by Fusarium and Alternaria spp.
Two genes conferring the brown midrib (bmr) trait had been backcrossed into six elite sorghum lines, resulting in reduced lignin in the bmr lines when compared with the wild-type parent. Seed and leaf tissue from field-grown plants, planted at two locations, were screened for Alternaria spp. and Fusarium spp. on semi-selective media. The results suggest that bmr lines do not have increased susceptibility to colonization by Alternaria spp. However, significantly fewer colonies of Fusarium spp., including Fusarium moniliforme, were recovered from seed of reduced lignin lines from two genetic backgrounds. That the bmr trait in some genetic backgrounds might enable increased resistance to colonization by F. moniliforme was further supported by greenhouse experiments in which peduncles of developing heads were inoculated with F. moniliforme. Mean lesion measurements on bmr lines were significantly lower than those resulting from inoculations on wild-type lines. Analysis of near-isogenic lines revealed that mean lesion lengths on bmr lines were significantly less than those produced on their wild-type counterparts in four of the six genetic backgrounds. These results suggest that reduced lignin lines exhibit, in some cases, increased resistance to Fusarium spp., including F. moniliforme.


Quick root searching method for resonances of dielectric optical microcavities with the boundary element method.
In this paper, we developed an efficient method for searching the resonant eigenfrequency of dielectric optical microcavities by the boundary element method. By transforming the boundary integral equation to a general eigenvalue problem for arbitrary, symmetric, and multi-domain shaped optical microcavities, we analyzed the regular motion of the eigenvalues against the frequency. The new strategy can predict multiple resonances, increase the speed of convergence, and avoid non-physical spurious solutions. These advantages greatly reduce the computation time in the search process of the resonances. Moreover, this method is not only valuable for dielectric microcavities, but is also suitable for other photonic systems with dissipations, whose resonant eigenfrequencies are complex numbers.


T cell activation Rho GTPase activating protein (TAGAP) is upregulated in clinical and experimental arthritis.
Genome-wide association studies have identified various susceptibility variants and loci associated with incidence of rheumatoid arthritis (RA) in different populations. One of these is T cell activation Rho GTPase activating protein (TAGAP). The present study sought to measure the expression of TAGAP in RA patients, CD4+ T cells subsets from healthy humans and in mice with collagen-induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and tissues of arthritic mice at different stages of the disease were used for the evaluation of TAGAP mRNA expression. Increased TAGAP expression was observed in RA patients compared to healthy controls, and there were differences in the expression level of TAGAP in the tissues of mice with experimental arthritis. Gene expression in CD4+ T cells from healthy humans was greatest 4 h after activation and protein expression was greatest after 24 h. The expression of TAGAP was not correlated with CD4+ lymphocyte subsets which were enriched for functionally defined subsets (Th17, Treg, Th1), further indicating its utility as an indicator of lymphocyte activation. These findings indicate that increased TAGAP expression is a distinguishing feature of inflammatory disease and further highlight the role of TAGAP in RA susceptibility.


Tristability in a light-actuated single-molecule magnet.
Molecules exhibiting bistability have been proposed as elementary binary units (bits) for information storage, potentially enabling fast and efficient computing. In particular, transition metal complexes can display magnetic bistability via either spin-crossover or single-molecule magnet behavior. We now show that the octahedral iron(II) complexes in the molecular salt [Fe(1-propyltetrazole)6](BF4)2, when placed in its high-symmetry form, can combine both types of behavior. Light irradiation under an applied magnetic field enables fully reversible switching between an S = 0 state and an S = 2 state with either up (M(S) = +2) or down (M(S) = -2) polarities. The resulting tristability suggests the possibility of using molecules for ternary information storage in direct analogy to current binary systems that employ magnetic switching and the magneto-optical Kerr effect as write and read mechanisms.


Deciding on access and levels of care: a comparison of Canada, Britain, Germany, and the United States.
Americans view universal coverage as a reality only if a minimum benefit package is explicitly defined, and discussions about expanding access take place under the slogan of minimum benefits. The policy environment is different in Canada, Britain, and Germany. There, health care costs are controlled and benefits provided under universal coverage plans. Yet the medical services provided in these countries result not from difficult decisions about rationing care at a "minimum" benefit level but from difficult political decisions about the structure of the health care system. Institutional factors rather than explicit policy influence the implicit health priorities in these countries. The United States, in contrast, develops policies that explicitly designate a minimum level of benefits.


Imparied maze performance in the rat caused by trimethyltin treatment: problem-solving deficits and perseveration.
Trimethyltin (TMT) produces cytological damage to several limbic-forebrain structures which is accompanied by behavioral changes including hyperactivity and aggressiveness. The purpose of this investigation was to determine whether the problem-solving capacity of the rat is affected by TMT treatment. Either 7.0 mg/kg of TMT ([CH3]3SnCl) or 0.9% saline was injected by gavage into the gastric lumen of each rat. The treated and non-treated animals were divided into two groups of nine each and tested subsequently on a series of Hebb-Williams maze problems. In comparison to the controls, the tin-treated rats made markedly more errors on all but one of the maze patterns. Moreover, the rate of error reduction across problems over the 10 daily trials was significantly retarded in the lesioned animals. In addition to these severe problem-solving deficits, the TMT-treated rat often exhibited a characteristic pattern of perseverative behavior while running in the maze. The pattern was not unlike stereotypies associated with the psychomotor pathology observed following treatment with certain drugs. Overall, the results of the performance of the animal in the Hebb-Williams task provides a corollary with the child afflicted with minimal brain dysfunction (MBD) and, thus, a model for MBD is suggested.


DNMT1 silencing affects locus specific DNA methylation and increases prostate cancer derived PC3 cell invasiveness.
DNMT1 maintains genomic DNA methylation at 5'-CpG-3' residues in somatic cells. Recent findings revealed that DNMT1 depletion causes distinct phenotypic changes in colon and gastric cancer cell lines, suggesting that the extent to which DNMT1 influences the expression of its target genes is cell-type specific. We determined the impact of DNMT1 depletion in prostate cancer derived cells on their gene expression profiles and cellular phenotype. Small interfering RNA was used to silence DNMT1 expression in prostate cancer derived PC3 cells (ATCC). The resulting cell line was validated by reverse transcriptase-polymerase chain reaction and Western blotting. Proliferation, migration and invasion assays were done in engineered cells to asses the effect of DNMT1 silencing on cellular phenotype. DNA microarrays were done to monitor changes in gene expression. Our data showed that DNMT1 loss dramatically decreased cell proliferation but significantly increased cell migratory and invasive potential. Additionally, in the limited set of genes whose expression and DNA methylation status were determined DNMT1 loss was associated with increased CDKN3 and claudin-3 expression, and also culminated in specific demethylation of Rb1 and RAR-beta promoters. These results show that the genetic and phenotypic consequences of silencing DNMT1 in PC3 cells are markedly different from those in colon and gastric cancers, indicating that DNMT1 preferentially targets certain gene promoters. Our findings also suggest that decreasing DNMT1 levels or activity can potentially enhance prostate cancer cell invasiveness.


Disability weights for the Global Burden of Disease 2013 study.
The Global Burden of Disease (GBD) study assesses health losses from diseases, injuries, and risk factors using disability-adjusted life-years, which need a set of disability weights to quantify health levels associated with non-fatal outcomes. The objective of this study was to estimate disability weights for the GBD 2013 study. We analysed data from new web-based surveys of participants aged 18-65 years, completed in four European countries (Hungary, Italy, the Netherlands, and Sweden) between Sept 23, 2013, and Nov 11, 2013, combined with data previously collected in the GBD 2010 disability weights measurement study. Surveys used paired comparison questions for which respondents considered two hypothetical individuals with different health states and specified which person they deemed healthier than the other. These surveys covered 183 health states pertinent to GBD 2013; of these states, 30 were presented with descriptions revised from previous versions and 18 were new to GBD 2013. We analysed paired comparison data using probit regression analysis and rescaled results to disability weight units between 0 (no loss of health) and 1 (loss equivalent to death). We compared results with previous estimates, and an additional analysis examined sensitivity of paired comparison responses to duration of hypothetical health states. The total analysis sample consisted of 30 230 respondents from the GBD 2010 surveys and 30 660 from the new European surveys. For health states common to GBD 2010 and GBD 2013, results were highly correlated overall (Pearson's r 0·992 [95% uncertainty interval 0·989-0·994]). For health state descriptions that were revised for this study, resulting disability weights were substantially different for a subset of these weights, including those related to hearing loss (eg, complete hearing loss: GBD 2010 0·033 [0·020-0·052]; GBD 2013 0·215 [0·144-0·307]) and treated spinal cord lesions (below the neck: GBD 2010 0·047 [0·028-0·072]; GBD 2013 0·296 [0·198-0·414]; neck level: GBD 2010 0·369 [0·243-0·513]; GBD 2013 0·589 [0·415-0·748]). Survey responses to paired comparison questions were insensitive to whether the comparisons were framed in terms of temporary or chronic outcomes (Pearson's r 0·981 [0·973-0·987]). This study substantially expands the empirical basis for assessment of non-fatal outcomes in the GBD study. Findings from this study substantiate the notion that disability weights are sensitive to particular details in descriptions of health states, but robust to duration of outcomes. European Centre for Disease Prevention and Control, Bill and Melinda Gates Foundation.


Laparoendoscopic single-site surgery in gynaecology: A new frontier in minimally invasive surgery.
REVIEW OBJECTIVE: To review the recent developments and published literature on laparoendoscopic single-site (LESS) surgery in gynaecology. Minimally invasive surgery has become a standard of care for the treatment of many benign and malignant gynaecological conditions. Recent advances in conventional laparoscopy and robotic-assisted surgery have favorably impacted the entire spectrum of gynaecological surgery. With the goal of improving morbidity and cosmesis, continued efforts towards refinement of laparoscopic techniques have lead to minimization of size and number of ports required for these procedures. LESS surgery is a recently proposed surgical term used to describe various techniques that aim at performing laparoscopic surgery through a single, small-skin incision concealed within the umbilicus. In the last 5 years, there has been a surge in the developments in surgical technology and techniques for LESS surgery, which have resulted in a significant increase in utilisation of LESS across many surgical subspecialties. Recently published outcomes data demonstrate feasibility, safety and reproducibility for LESS in gynaecology. The contemporary LESS literature, extent of gynaecological procedures utilising these techniques and limitations of current technology will be reviewed in this manuscript. LESS surgery represents the newest frontier in minimally invasive surgery. Comparative data and prospective trials are necessary in order to determine the clinical impact of LESS in treatment of gynaecological conditions.


Weighted pseudometric discriminatory power improvement using a Bayesian logistic regression model based on a variational method.
In this paper, we investigate the effectiveness of a Bayesian logistic regression model to compute the weights of a pseudo-metric, in order to improve its discriminatory capacity and thereby increase image retrieval accuracy. In the proposed Bayesian model, the prior knowledge of the observations is incorporated and the posterior distribution is approximated by a tractable Gaussian form using variational transformation and Jensen's inequality, which allow a fast and straightforward computation of the weights. The pseudo-metric makes use of the compressed and quantized versions of wavelet decomposed feature vectors, and in our previous work, the weights were adjusted by classical logistic regression model. A comparative evaluation of the Bayesian and classical logistic regression models is performed for content-based image retrieval as well as for other classification tasks, in a decontextualized evaluation framework. In this same framework, we compare the Bayesian logistic regression model to some relevant state-of-the-art classification algorithms. Experimental results show that the Bayesian logistic regression model outperforms these linear classification algorithms, and is a significantly better tool than the classical logistic regression model to compute the pseudo-metric weights and improve retrieval and classification performance. Finally, we perform a comparison with results obtained by other retrieval methods.


Salicylic acid is an uncoupler and inhibitor of mitochondrial electron transport.
The effect of salicylic acid (SA) on respiration and mitochondrial function was examined in tobacco (Nicotiana tabacum) suspension cell cultures in the range of 0.01 to 5 mm. Cells rapidly accumulated SA up to 10-fold of the externally applied concentrations. At the lower concentrations, SA accumulation was transitory. When applied at 0.1 mm or less, SA stimulated respiration of whole cells and isolated mitochondria in the absence of added ADP, indicating uncoupling of respiration. However, at higher concentrations, respiration was severely inhibited. Measurements of ubiquinone redox poise in isolated mitochondria suggested that SA blocked electron flow from the substrate dehydrogenases to the ubiquinone pool. This inhibition could be at least partially reversed by re-isolating the mitochondria. Two active analogs of SA, benzoic acid and acetyl-SA, had the same effect as SA on isolated tobacco mitochondria, whereas the inactive p-hydroxybenzoic acid was without effect at the same concentration. SA induced an increase in Aox protein levels in cell suspensions, and this was correlated with an increase in Aox1 transcript abundance. However, when applied at 0.1 mM, this induction was transient and disappeared as SA levels in the cells declined. SA at 0.1 mM also increased the expression of other SA-responsive genes, and this induction was dependent on active mitochondria. The results indicate that SA is both an uncoupler and an inhibitor of mitochondrial electron transport and suggest that this underlies the induction of some genes by SA. The possible implications of this for the interpretation of SA action in plants are discussed.


Racial disparities and considerations for active surveillance of prostate cancer.
Active surveillance (AS) for the management of low-risk prostate cancer has been increasing and in the general population appears safe, allowing for a reduction in the harms of prostate cancer screening such as overtreatment. African-American (AA) men have overall worse outcomes from prostate cancer compared to Caucasian-American (CA) men for a variety of socioeconomic, cultural and possibly biologic reasons, thus complicating the use of AS in this population. Strategies for optimizing care and mitigating risk in this population include pursuing close surveillance with steadfast patient compliance, the use of multiparametric MRI with targeted biopsies including the anterior prostate to reduce the risk of undersampling, as well as a judicious and thoughtful incorporation of novel molecular biomarkers for risk stratification. Currently, there exists no direct data to suggest that AS cannot be safely carried out in AA men following an informed discussion and after engaging in shared decision making. Physicians should have a low threshold for consideration of definitive therapy. Additional efforts should be made in increasing the engagement of minority participants in clinical trials, to gain an improved representation of underserved populations in future research.


Biomimetic recognition and immunochemical assay of ligand binding to collagen.
The objectives of this investigation were to analyze the adhesive interactions between type 1 collagen and two hydrophilic monomer primers (ligands) for dentin bonding through computer modeling and a novel immunochemical binding assay method. The hydrophilic monomers studied included 2-hydroxyethyl methacrylate (HEMA) and 2-acryloyloxyethyl phosphate (PA). For computer modeling studies, a triple helical model structure of collagen fibril extracted from a public domain Protein Data Bank was used. The ligand conformations were modeled and optimized by Sybyl, and their interactions with the triple helical collagen structure in a solvent environment of water were simulated by AutoDock software. The effect of ligand binding to subsequent monoclonal antibody binding was also studied using an immunochemical binding assay method developed by us. The computer simulation results and binding assay results were analyzed for relationships pertinent to collagen-ligand interaction in bonding of dentin primers to demineralized dentin. Computer docking results indicate that ligand binding to collagen is favored to occur at cavity sites on the collagen molecular surfaces, where steric and electrostatic effects may play a critical role in mediating van der Waals and Coulombic interactions between ligand and receptor molecules. Prior ligand exposure of collagen reduces subsequent antibody binding during in vitro experiments. Differences in antibody binding were observed both as a function of ligand type and its concentration. Both steric complementarity and electrostatic complementarity conditions were observed in the docking site selection. Under conditions of ligand binding, antibody binding is diminished as a function of ligand structure and its concentration. The results suggest that approaches combining computer modeling and in vitro binding assay methods are powerful tools in evaluating dentinal adhesion at the atomic and/or molecular level.