Apochromatic telescope without anomalous dispersion glasses.
In order to correct secondary longitudinal chromatic aberration in conventional refracting optical systems, it is necessary to use at least one optical material having anomalous partial dispersion. A novel lens system with correction of the secondary spectrum by using only normal glasses is presented. The lens system comprises three widely separated lens components; both second and third components are subaperture. The presented example of an apochromatic telescope demonstrates secondary spectrum correction with the use of only crown BK7 and flint F2, which are among the most inexpensive optical glasses available at the market. Two more similar designs are presented, both with the use of low-cost slightly anomalous dispersion glasses. These telescopes have a higher relative aperture and a smaller tertiary spectrum.


Controllable generation and manipulation of micro-bubbles in water with absorptive colloid particles by CW laser radiation.
Micrometer-sized vapor-gas bubbles are formed due to local heating of a water suspension containing absorptive pigment particles of 100 nm diameter. The heating is performed by CW near-infrared (980 nm) laser radiation with controllable power, focused into a 100 μm spot within a 2 mm suspension layer. By changing the laser power, four regimes are realized: (1) bubble generation; (2) stable growth of the existing bubbles; (3) stationary existence of the bubbles and (4) the bubbles' shrinkage and collapse. This behavior is interpreted based on the temperature conditions. The generation and evolution of single bubbles and ensembles of bubbles with controllable sizes and numbers is demonstrated. The bubbles are grouped within the laser-illuminated region and form quasi-ordered structures. They can easily be moved and transported controlled by the focal spot. The results are useful for applications associated with the precise manipulation, sorting and specific delivery in nano- and micro-engineering problems.


A Bayesian framework for inference of the genotype-phenotype map for segregating populations.
Complex genetic interactions lie at the foundation of many diseases. Understanding the nature of these interactions is critical to developing rational intervention strategies. In mammalian systems hypothesis testing in vivo is expensive, time consuming, and often restricted to a few physiological endpoints. Thus, computational methods that generate causal hypotheses can help to prioritize targets for experimental intervention. We propose a Bayesian statistical method to infer networks of causal relationships among genotypes and phenotypes using expression quantitative trait loci (eQTL) data from genetically randomized populations. Causal relationships between network variables are described with hierarchical regression models. Prior distributions on the network structure enforce graph sparsity and have the potential to encode prior biological knowledge about the network. An efficient Monte Carlo method is used to search across the model space and sample highly probable networks. The result is an ensemble of networks that provide a measure of confidence in the estimated network topology. These networks can be used to make predictions of system-wide response to perturbations. We applied our method to kidney gene expression data from an MRL/MpJ × SM/J intercross population and predicted a previously uncharacterized feedback loop in the local renin-angiotensin system.


Ergodic capacity comparison of optical wireless communications using adaptive transmissions.
Ergodic capacity is investigated for the optical wireless communications employing subcarrier intensity modulation with direct detection, and coherent systems with and without polarization multiplexing over the Gamma-Gamma turbulence channels. We consider three different adaptive transmission schemes: (i) variable-power, variable-rate adaptive transmission, (ii) complete channel inversion with fixed rate, and (iii) truncated channel inversion with fixed rate. For the considered systems, highly accurate series expressions for ergodic capacity are derived using a series expansion of the modified Bessel function and the Mellin transformation of the Gamma-Gamma random variable. Our asymptotic analysis reveals that the high SNR ergodic capacities of coherent, subcarrier intensity modulated, and polarization multiplexing systems gain 0.33 bits/s/Hz, 0.66 bits/s/Hz, and 0.66 bits/s/Hz respectively with 1 dB increase of average transmitted optical power. Numerical results indicate that a polarization control error less than 10° has little influence on the capacity performance of polarization multiplexing systems.


Pulmonary artery constriction produces a greater right ventricular dynamic afterload than lung microvascular injury in the open chest dog.
Investigators model noncardiogenic pulmonary hypertension by constricting the pulmonary artery to increase right ventricular afterload. To investigate this model's validity, we compared the right ventricular afterload, quantified as pulmonary input impedance, created by constricting the pulmonary artery and by inducing a pulmonary microvascular injury (with glass beads infused into the pulmonary circulation). The pulmonary injury constriction produced a different right ventricular afterload than the microvascular injury. The constriction increased both the input resistance and the characteristic impedance. Microvascular injury increased only input resistance. Physiological levels of lung inflation did not influence pulmonary impedance, but lung hyperinflation increased input resistance both before and while constricting the pulmonary artery or after producing microvascular injury. Total right ventricular power output and stroke work were unchanged during each vascular intervention. Pulmonary artery constriction did not affect power output distribution, whereas microvascular injury decreased oscillatory power and its relative contribution to total power. Lung hyperinflation dramatically reduced right ventricular power and left ventricular stroke work. These effects appeared mediated by right ventricular afterload increase uncompensated for by right ventricular preload increase. These observations help explain the hemodynamic consequences of acute pulmonary hypertension and the effects of lung hyperinflation with positive end-expiratory pressure respiration in such patients.


Economic and Public Health Impacts of Policies Restricting Access to Hepatitis C Treatment for Medicaid Patients.
Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C. Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice-only advanced disease is treated before Medicare eligibility and 2) Full Access-both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from $5,369 to $11,960 and in effectiveness from 0.82 to 3.01 quality-adjusted life-years. In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared with Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients. Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full-access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment.


The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties.
CD3 antibodies are proven immunosuppressants capable of reversing transplant rejection episodes. Their general application has been limited both by their immunogenicity and, in particular, by the "first-dose" cytokine-release syndrome experienced by patients after the initial administration of antibody. We have produced a set of variants of the humanized YTH 12.5 CD3 monoclonal antibody (mAb) (Routledge et al., Eur. J. Immunol. 1991. 21: 2717) bearing different human heavy (H) chain constant regions, with the intention of finding a form of the antibody that is not able to activate T cells. Comparison of the variants having gamma 1, gamma 2, gamma 3 and gamma 4 H chains in a competitive binding assay showed that antibody avidity was not affected by IgG subclass. Using a sensitive indicator of FcR binding activity (the capacity of the CD3 mAb to redirect cytotoxic T cells to kill the monocytic cell line U-937) we demonstrated a functional hierarchy of gamma 1 = gamma 4 > alpha 2 =/> gamma 3 mb >> gamma 2. An aglycosyl version of the gamma 1 CD3 mAb, produced by site-directed mutagenesis (Asn297 to Ala), still had considerable activity in this assay (intermediate to the gamma 1 and alpha 2 CD3 mAb), albeit at a level approximately 10-fold lower than that of the parental gamma 1 form. When we tested their ability to stimulate T cell proliferation in vitro in the presence of 5% human serum, all of the wild-type immunoglobulin isotypes were found to be active, although there were T cell donor-dependent variations in the extent of the responses. The aglycosyl gamma 1 mAb was, however, completely non-mitogenic in all of ten donors tested, unless the assay was performed in IgG-free medium. Despite being non-stimulatory, this mAb was also able to inhibit the mixed lymphocyte reaction responses of both naive and primed T cells. Comparison of the gamma 1 and aglycosyl gamma 1 mAb in an experimental mouse model for CD3 mAb-induced cytokine release indicated that removal of the carbohydrate moiety from the gamma 1 constant region reduced the in vivo tumor necrosis factor-alpha response by a factor of at least 16-fold. These data suggest that the aglycosyl gamma 1 CD3 mAb is a promising candidate for immunosuppressive therapy without "first dose" side effects.


[Atypical Hemolytic Uremic Syndrome: experience of a pediatric center].
In the last two years we admitted in our Hospital 38 children with acute renal failure (ARF). Six of them were affected by hemolytic uremic syndrome (HUS) atypical. The aHUS is diagnosed in the presence of thrombotic microangiopathy (MAT), renal insufficiency (GFR 5%). The clinical presentation of our children has been varied and so also its evolution. Patients observed were all male, aged 2 to 12 years, and no one had a family history of kidney disease. In four patients we documented alterations of complement factors (MCP deficiency and factor H and presence of anti factor H). Repeated blood transfusions were required in 4 patients and in 3 patients the platelet count was slightly reduced. In 5 patients we did plasmapheresis and in 3 patients dialysis (hemodialysis and peritoneal dialysis). In three patients in whom the diagnosis was not clear, renal biopsy was performed to confirm the diagnosis. Eculizumab was administered in 3 patients resistant to plasma exchange. We obtain a rapid response on MAT with normalization of platelet count. The effect on renal function was variable (complete remission in a patient, partial improvement in another, and unresponsiveness in the last). The last had on Kidney biopsy signs of severe impairment and we documented the presence of antibodies to eculizumab. HUS is a rare condition, but probably much more common than reported. In children with ARF and microangiopathic anemia is necessary evaluated complement factors as early to obtain an improved clinical response to treatment with eculizumab.


Emergency medical services responders' perceptions of the effect of stress and anxiety on patient safety in the out-of-hospital emergency care of children: a qualitative study.
Prehospital emergency medical services (EMS) providers report anxiety as the second most common contributor to paediatric patient safety events. The objective of this study was to understand how EMS providers perceive the effect of stress and anxiety on paediatric out-of-hospital patient safety. This was a nationwide study of EMS providers from 44 of 50 (88%) US states. A total of 753 eligible EMS professionals, including emergency medical technicians, emergency department physicians and nurses (general and paediatric), and respiratory therapists who participate in out-of-hospital transports. Outcomes included responses to: (1) clinical situations where heightened stress or anxiety was likely to contribute to safety events, (2) aspects of these clinical situations that cause stress or anxiety and (3) how stress or anxiety may lead to paediatric safety events. EMS providers reported that the clinical situations where stress and anxiety were more likely to contribute to paediatric patient safety events were trauma, respiratory distress and cardiac issues. Key themes were: (1) provider sympathy or identification with children, (2) difficulty seeing an innocent child hurt and the inherent value of children and (3) insufficient exposure to paediatric emergencies. Caring for paediatric emergencies creates unique stresses on providers that may affect patient safety. Many of the factors reported to cause provider stress and anxiety are inherent attributes of children and therefore not modifiable. Tools that support care during stressful conditions such as cognitive aids may help to mitigate anxiety in the prehospital care of children. Further research is needed to identify opportunities for and attributes of interventions.


Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831.
The efficacy of trastuzumab for metastases coupled with the relatively poor prognosis of patients with node-positive, HER2-positive breast cancer has led to the evaluation of trastuzumab as an adjuvant therapy. A prospective, randomized, three-arm, phase III trial is being conducted by the Breast Intergroup (N9831) for women with primary, operable, histologically confirmed, node-positive breast carcinoma that strongly overexpresses (3+) HER2 protein and/or displays HER2/neu gene amplification, as determined by local laboratory testing. The protocol requires confirmatory central testing of HER2 status using the HercepTest immunohistochemistry and the Vysis PathVysion fluorescence in situ hybridization (FISH) assays. Tumor specimens from the first 119 patients enrolled in N9831 were centrally tested; 74% were found to be HercepTest 3+ and 66% were found to have HER2 gene amplification. Only six of nine (67%) of the specimens submitted by local laboratories as FISH positive could be confirmed by central assays. The concordance for central HercepTest and central FISH assays was 92%. The poor concordance (74%) between local and central testing for HER2 status has led to modifications in the eligibility criteria for N9831.


Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria.
Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the pH-independent role of bicarbonate on glutamine and glutamate metabolism. Changes in the concentration of key intermediates and products during the incubations were used to calculate metabolite flux rates through specific mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as substrates, bicarbonate caused an inhibition of glutamate oxalacetate transaminase flux and a stimulation of glutamate deamination. The same effects were also produced with addition of either aminooxyacetate or malonate. These effects of bicarbonate were prevented when 0.2 mM malate was included as an additional substrate. Bicarbonate ion was identified as a potent competitive inhibitor of rat kidney cortex succinate dehydrogenase. These results indicate that aminooxyacetate, malonate, and bicarbonate all act to stimulate glutamate deamination through a suppression of glutamate transamination, and that the control by transamination of glutamate deamination is due to alterations in alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with glutamine in the absence of glutamate, bicarbonate was found to inhibit glutamate dehydrogenase flux. This effect was found to be due in part to the lower intramitochondrial pH observed in incubations with bicarbonate. These findings indicate that bicarbonate ion, independent of pH, may have an important regulatory role in renal glutamine and glutamate metabolism.


Genomics-driven discovery of a linear lipopeptide promoting host colonization by endofungal bacteria.
The rice seedling blight fungus Rhizopus microsporus weakens or kills plants by means of a potent toxin produced by endobacteria (Burkholderia rhizoxinica) that live within the fungal hyphae. The success of the highly attuned microbial interaction is partly based on the bacteria's ability to roam and re-colonize the fungal host. Yet, apart from the toxin, chemical mediators of the symbiosis have remained elusive. By genome mining and comparison we identified a cryptic NRPS gene cluster that is conserved among all sequenced Rhizopus endosymbionts. Metabolic profiling and targeted gene inactivation led to the discovery of a novel linear lipopeptide, holrhizin A, which was fully characterized. Through in vitro and in vivo assays we found that holrhizin acts (A) as a biosurfactant to reduce surface tension, (B) influences the formation of mature biofilms and thus cell motility behavior that ultimately supports the bacterial cells to (C) colonize and invade the fungal host, consequently supporting the re-establishment of the exceptional Burkholderia-Rhizopus symbiosis. We not only unveil structure and function of an linear lipopeptide from endofungal bacteria but also provide a functional link between the symbiont's orphan NRPS genes and a chemical mediator that promotes bacterial invasion into the fungal host.


Aerobiology of sweet chestnut (Castanea sativa Mill.) in north-west Croatia.
The aims of the study were to analyse characteristics of the Castanea airborne pollen and to compare aeropalynological data obtained from two sampling stations in north-west Croatia. The study was conducted in Zagreb and Samobor during the 2003-2006 periods, using the seven-day volumetric samplers of the Hirst design. In both study areas, the seasons of chestnut pollination were similar and lasted from June to the end of July, which is comparable to other European cities. A general rule was noticed--the shorter the main pollen season, the higher the pollen peak concentration. Although the pollen season of Fagales pollen is prolonged to summer in the area of inland west-north Croatia due to the genus Castanea summer pollination, the number of days with pollen air concentration higher than 50 per m3 was low and was not likely to have any major effects in allergic individuals. Airborne pollen concentration of Castanea showed positive statistically significant correlation with air temperature and negative non-significant correlation with precipitation. Because of the non-significant differences between the two stations, for a possible long-term forecast model for Fagales airborne pollen for this part of north-west Croatia, aerobiological data obtained from only one station are sufficient.


Studying essential DNA metabolism proteins in Xenopus egg extract.
The correct duplication of genetic information is essential to maintain genome stability, which is lost in cancer cells. Replication fork integrity is ensured by a number of DNA metabolism proteins that assist replication of chromatin regions difficult to replicate due to their intrinsic DNA sequence composition, coordinate repair of DNA molecules resulting from aberrant replication events or protect replication forks in the presence of lesions impairing their progression. Some DNA metabolism genes involved in DNA repair are essential in higher eukaryotes even in unchallenged conditions, suggesting the existence of biological processes requiring these specialized functions in organisms with complex genomes. The impact on cell survival of null mutants of many DNA metabolism genes has precluded complete in depth analysis of their function. Cell free extracts represent a fundamental tool to overcome survival issues. The Xenopus laevis egg cell free extract is an ideal system to study replication-associated functions of essential genes. We are taking advantage of this system together with innovative imaging and proteomic based experimental approaches to characterize the molecular function of essential DNA metabolism proteins. Using this approach we have uncovered the role of some essential homologous recombination and fork protection proteins in chromosomal DNA replication and we have characterized some of the factors required for faithful replication of specific vertebrate genomic regions. This approach will be instrumental to study the molecular mechanisms underlying the function of a number of essential DNA metabolism proteins involved in the maintenance of genome stability in complex genomes.


Arsenic remobilization in a shallow lake: the role of sediment resuspension.
Oxic resuspension occurs regularly in shallow lakes, yet its role as a mechanism for contaminant remobilization remains ill defined. This study investigated contaminant remobilization during sediment resuspension and determined whether changes in contaminant sediment partitioning reflected the mechanisms controlling remobilization. Arsenic-contaminated sediment from a shallow wetland was subjected to simulated resuspension under a range of differing initial pH conditions. The effect of resuspension on As partitioning was evaluated using a fractionation scheme targeting the dissolved, ion exchangeable, carbonate, organic, amorphous iron oxide, crystalline iron oxide, and apatite fractions. Rate investigations demonstrated that arsenic remobilization occurred on timescales similar to resuspension events, with concentrations reaching steady state within 24 h. The sediment also buffered slurry pH to 8.3 in experiments where the initial pH was between 4 and 10. This pH regulation was attributed to carbonate dissolution or acid-base equilibria of surface base functional groups, although iron oxide and organic matter dissolution did occur in experiments with an initial pH outside this range. Remobilization caused losses in arsenic associated with the ion exchangeable, organic, and amorphous iron fractions but changes in initial pH have a negligible effect on arsenic remobilization or partitioning within the well-buffered region. Resuspension released approximately 20% of the total sediment arsenic, although calculations indicated that a single resuspension event would not significantly change water column arsenic concentrations. While not conclusively proving the mechanisms of remobilization, fractionation gave valuable insight into the effect of sediment resuspension on contaminant remobilization.


Diagnostic heterogeneity in psychiatry: towards an empirical solution.
The launch of the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has sparked a debate about the current approach to psychiatric classification. The most basic and enduring problem of the DSM is that its classifications are heterogeneous clinical descriptions rather than valid diagnoses, which hampers scientific progress. Therefore, more homogeneous evidence-based diagnostic entities should be developed. To this end, data-driven techniques, such as latent class- and factor analyses, have already been widely applied. However, these techniques are insufficient to account for all relevant levels of heterogeneity, among real-life individuals. There is heterogeneity across persons (p:for example, subgroups), across symptoms (s:for example, symptom dimensions) and over time (t:for example, course-trajectories) and these cannot be regarded separately. Psychiatry should upgrade to techniques that can analyze multi-mode (p-by-s-by-t) data and can incorporate all of these levels at the same time to identify optimal homogeneous subgroups (for example, groups with similar profiles/connectivity of symptomatology and similar course). For these purposes, Multimode Principal Component Analysis and (Mixture)-Graphical Modeling may be promising techniques.


Climate models fail to capture strengthening wintertime North Atlantic jet and impacts on Europe.
Projections of wintertime surface climate over Europe depend on reliable simulations of the North Atlantic atmospheric circulation from climate models. However, it is unclear whether these models capture the long-term observed trends in the North Atlantic circulation. Here, we show that over the period from 1951 to 2020, the wintertime North Atlantic jet has strengthened, while model trends are, on average, only very weakly positive. The observed strengthening is greater than in any one of the 303 simulations from 44 climate models considered in our study. This divergence between models and observations is now much more apparent because of a very strong jet observed over the past decade. The models similarly have difficulty capturing the observed precipitation trends over Europe. Our results suggest that projections of winter atmospheric circulation and associated precipitation over Europe may be unreliable because they fail to capture the response to human emissions or underestimate the magnitude of multidecadal-to-centennial time scale internal variability.


A randomized trial of face-to-face counselling versus telephone counselling versus bibliotherapy for occupational stress.
The aim of the present study was to compare the effectiveness and acceptability of three interventions for occupational stress. A total of 90 National Health Service employees were randomized to face-to-face counselling or telephone counselling or bibliotherapy. Outcomes were assessed at post-intervention and 4-month follow-up. Clinical Outcomes in Routine Evaluation (CORE), General Health Questionnaire (GHQ-12), and Perceived Stress Scale (PSS-10) were used to evaluate intervention outcomes. An intention-to-treat analyses was performed. Repeated measures analysis revealed significant time effects on all measures with the exception of CORE Risk. No significant group effects were detected on all outcome measures. No time by group significant interaction effects were detected on any of the outcome measures with the exception of CORE Functioning and GHQ total. With regard to acceptability of interventions, participants expressed a preference for face-to-face counselling over the other two modalities. Overall, it was concluded that the three intervention groups are equally effective. Given that bibliotherapy is the least costly of the three, results from the present study might be considered in relation to a stepped care approach to occupational stress management with bibliotherapy as the first line of intervention, followed by telephone and face-to-face counselling as required.


Family-initiated dialogue about medications during family-centered rounds.
Experts suggest family engagement in care can improve safety for hospitalized children. Family-centered rounds (FCRs) can offer families the opportunity to participate in error recovery related to children's medications. The objective of this study was to describe family-initiated dialogue about medications and health care team responses to this dialogue during FCR to understand the potential for FCR to foster safe medication use. FCR were video-recorded daily for 150 hospitalized children. Coders sorted family-initiated medication dialogue into mutually exclusive categories, reflecting place of administration, therapeutic class, topic, and health care team responses. Health care team responses were coded to reflect intent, actions taken by the team, and appropriateness of any changes. Eighty-three (55%) of the 150 families raised 318 medication topics during 347 FCR. Most family-initiated dialogue focused on inpatient medications (65%), with home medications comprising 35%. Anti-infectives (31%), analgesics (14%), and corticosteroids (11%) were the most commonly discussed medications. The most common medication topics raised by families were scheduling (24%) and adverse drug reactions (11%). Although most health care team responses were provision of information (74%), appropriate changes to the child's medications occurred in response to 8% of family-initiated dialogue, with most changes preventing or addressing adverse drug reactions or scheduling issues. Most families initiated dialogue regarding medications during FCRs, including both inpatient and home medications. They raised topics that altered treatment and were important for medication safety, adherence, and satisfaction. Study findings suggest specific medication topics that health care teams can anticipate addressing during FCR.


Perioperative statin therapy is not associated with reduced risk of anastomotic leakage after colorectal resection.
Anastomotic leakage is a serious complication of colorectal surgery. Several studies have demonstrated the beneficial pleiotropic effects of statins, and preliminary studies have suggested that perioperative statin treatment may be associated with reduced risk of anastomotic leakage. We aimed to investigate whether perioperative statin therapy was associated with a reduced anastomotic leakage rate after colorectal resections with primary anastomosis. The study was based on prospectively collected data from the Danish Colorectal Cancer Group and electronically registered medical records holding information on perioperative statin therapy. Data were collected from the 6 major surgical centers responsible for all elective colorectal cancer surgery in the eastern part of Denmark. We collected data on 2766 patients with electronically registered medical records who underwent resection of the colon or rectum with primary anastomosis from 2006 to 2009. The primary outcome measured was anastomotic leakage requiring surgical intervention. Five hundred eighteen patients (19%) were treated with statins perioperatively. Four hundred ninety-six patients received statins both before and after surgery. Fifty-two patients (10.5%) received high-dose statin therapy. Possible risk factors for anastomotic leakage were identified via univariate regression analyses. In subsequent multivariate analysis, perioperative statin therapy was not associated with reduced anastomotic leakage rate (OR (95% CI) 1.31 (0.84-2.05), p = 0.23). We identified intraoperative blood transfusion, rectal resection (versus colonic), male sex, and tobacco usage as risk factors for anastomotic leakage in the multivariate analysis. This study is limited by its observational design and missing data on comorbidities and BMI. Perioperative statin therapy was not significantly associated with reduced anastomotic leakage rate after colorectal resection with primary anastomosis.


Potentially toxic element fractionation in technosoils using two sequential extraction schemes.
This study reports the chemical fractionation of several potentially toxic elements (Zn, Pb, Cd, As, and Sb) in contaminated technosoils of two former smelting and mining areas using two sequential extraction schemes. The extraction schemes used in this study were the Tessier's scheme and a modified BCR scheme. The fractions were rearranged into four equivalent fractions defined as acid soluble, reducible, oxidizable, and residual to compare the results obtained from two sequential extraction schemes. Surface soils were samples from a waste landfill contaminated with Zn, Pb, and Cd located at Mortagne-du-Nord (MDN; North France) and from a settling basin contaminated with PTE such as As, Pb, and Sb located at La Petite Faye (LPF; Limoges, France). The study of the Zn, Pb, Cd, As, and Sb partitioning in the acid soluble, reducible, oxidizable, and residual fractions of the technosoils revealed that Zn, Cd, and Pb were mainly associated with the acid soluble and reducible fractions for MDN site, while As, Sb, and Pb were associated with residual fraction for LPF site. Fractionation results indicate that the percentages of Zn, Pb, Cd, As, and Sb extracted in Fe-Mn oxide bound fraction of Tessier's scheme were always higher than those extracted by modified BCR scheme. This may be attributed to the stronger Tessier's scheme conditions used to extract this fraction. In contrast the percentages of Zn, Pb, Cd, As, and Sb extracted in the organic fraction of the modified BCR scheme were always higher than those of the Tessier's scheme. The order of mobility of PTE was as follows: Cd > Zn > Pb in MDN site and As > Sb > Pb in LPF site. PTE were distributed in all soil fractions, with the most relevant enrichments in extractable and residual fractions. A significant amount of Cd, Pb, and Zn were rather mobile, which suggests that these elements can be readily available to plants and soil organisms.


Synthetic mesh repair of an anterior perineal hernia following robotic radical urethrocystectomy.
Perineal hernia is a protrusion of intra-abdominal viscera through a defect in the pelvic floor and is a rare but challenging complication after extensive abdominoperineal surgery. There have been small series published after colorectal exenteration, but no cases have been reported after radical cystectomy and urethrectomy. A 68 years old woman developed an anterior perineal hernia, with no vaginal prolapse, after an anterior exenteration for bladder cancer. A perineal approach with the use of a synthetic polypropylene mesh was chosen to resolve the condition. After 6 months of follow-up, the patient has no symptoms or recurrence of the anterior perineal hernia. To our knowledge, this case is the first report of perineal hernia after radical urethrocystectomy. Although being a case report, this article describes a potential and challenging complication after extensive anterior pelvic surgery, that could increase its incidence in the future. Literature review shows that whether perineal, abdominal or combined approach is chosen, surgery must respect hernia repair principles.


Selective carbon dioxide sorption by a new breathing three-dimensional Zn-MOF with Lewis basic nitrogen-rich channels.
Lewis basic heteroatoms orderly located inside the well-defined channels of metal-organic frameworks (MOFs) are potentially ideal active sites for selective gas sorption and catalysis. To develop functional MOFs with Lewis basic sites inside channels, a new C2h-symmetric dicarboxylate-based bridging ligand, 3,3'-(pyrazine-2,5-diyl)dibenzoic acid (3,3'-PDBA), was prepared by a Suzuki coupling reaction. Subsequently, two new Zn-MOFs containing the C2h-symmetric 3,3'-PDBA bridging ligand and two different bis(pyridyl)-based pillars, 1,2-bis(4-pyridyl)ethane (bpa) or 1,2-bis(4-pyridyl)ethylene (bpe), were prepared through a thermal reaction in N,N-dimethylformamide (DMF). The resulting two Zn-MOFs of the general formula of three-dimensional (3D) [Zn2(μ4-3,3'-PDBA)2(μ2-bpa)]3·(DMF)5(H2O)13 (1) or 3D-like 2D [Zn2(μ4-3,3'-PDBA)2(μ2-bpe)]·(H2O) (2) displayed primitive cubic pcu net and 2D sql net, respectively. Both Zn-MOFs 1 and 2 contain uncoordinated Lewis basic pyrazinyl nitrogen atoms in the frameworks. The solvent-free 1 with flexible bpa linkers only showed a potential porosity of 15.9% by PLATON analysis. Zn-MOF 1 with openly accessible Lewis basic sites exhibited selective sorption of CO2 over N2, H2, and CH4 at low temperature. The adsorption and desorption isotherms for CO2 sorption at 196 K showed phenomenal hysteretic behaviour indicative of a breathing process through an adsorbate-discriminatory gate-opening process toward CO2 at a low gas pressure.


Acute vascular endothelial growth factor expression during hypertrophy is muscle phenotype specific and localizes as a striated pattern within fibres.
Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors that promote myofibre growth and concurrent adaptive changes in the microvasculature. These studies tested the hypothesis that vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth factor (HB-EGF) expression are upregulated during the early stages of compensatory muscle growth induced by chronic functional overload (FO). Bilateral FO of the plantaris and soleus muscles was induced for 3 or 7 days in the hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with control (non-FO) rats. Relative muscle mass (in mg (kg body weight)(-1)) increased by 18 and 24% after 3 days and by 20 and 33% after 7 days in the plantaris and soleus muscles, respectively. No differences in HB-EGF mRNA or protein were observed in either muscle of FO rats relative to control muscles. The VEGF mRNA was similar in the soleus muscles of FO and control rats, whereas a significant elevation occurred at 3 and 7 days of FO in the plantaris muscle. However, VEGF protein expression after 3 days of FO exhibited a differential response; expression in the soleus muscle decreased 1.6-fold, whereas that in the plantaris muscle increased 1.8-fold compared with the control muscle. After 7 days of FO, VEGF protein remained elevated within the plantaris muscle, but returned to basal levels in the soleus. Robust basal HB-EGF and VEGF protein expression was consistently seen in control muscles. In all groups, immunohistochemistry for VEGF protein displayed a distinct striated expression pattern within myofibres, with considerably less labelling in extracellular spaces. Constitutive expression of HB-EGF and VEGF in control myofibres is consistent with housekeeping roles for these growth factors in skeletal muscle tissue. However, the specific patterns of VEGF expression in these muscles during FO may reflect the chronic changes in neural recruitment between muscles and the co-ordination of angiogenic and/or other hypertrophic responses.


Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased Mortality, Increased Blood Product Use, and Greater Hospital Resource Consumption: A Pilot Investigation.
Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality. All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days. The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P < .01). Receiver operator curve analysis identified inflection points in mortality outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%) had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme hypocalcemia and hypercalcemia also received more red blood cells, plasma, platelets, and calcium repletion. Hypocalcemia and hypercalcemia occur commonly during the initial resuscitation of severely injured patients. Mild hypocalcemia may be tolerable, but more extreme hypocalcemia and any hypercalcemia should be avoided. Further assessment to define best practice for calcium management during resuscitation is warranted.


Effect of mindfulness meditation on brain-computer interface performance.
Electroencephalogram based brain-computer interfaces (BCIs) enable stroke and motor neuron disease patients to communicate and control devices. Mindfulness meditation has been claimed to enhance metacognitive regulation. The current study explores whether mindfulness meditation training can thus improve the performance of BCI users. To eliminate the possibility of expectation of improvement influencing the results, we introduced a music training condition. A norming study found that both meditation and music interventions elicited clear expectations for improvement on the BCI task, with the strength of expectation being closely matched. In the main 12 week intervention study, seventy-six healthy volunteers were randomly assigned to three groups: a meditation training group; a music training group; and a no treatment control group. The mindfulness meditation training group obtained a significantly higher BCI accuracy compared to both the music training and no-treatment control groups after the intervention, indicating effects of meditation above and beyond expectancy effects.


Glycophorin A somatic cell mutation frequencies in Finnish reinforced plastics workers exposed to styrene.
We have used the glycophorin A (GPA) in vivo somatic cell mutation assay to assess the genotoxic potential of styrene exposure in 47 reinforced plastics workers occupationally exposed to styrene and 47 unexposed controls matched for age, gender, and active smoking status. GPA variant erythrocyte frequencies (Vf), reflecting GPA allele loss (phi/N) and allele loss and duplication (N/N) somatic mutations arising in vivo in the erythroid progenitor cells of individuals of GPA M/N heterozygous genotype, were flow cytometrically determined in peripheral blood samples from these subjects. Measurements of styrene exposure of the workers at the time of blood sampling showed a mean 8-h time-weighted average (TWA8-h) styrene concentration of 155 mg/m3 (37 ppm) in the breathing zone. Mean urinary concentrations of the styrene metabolites mandelic acid (MA) and mandelic acid plus phenyl glyoxylic acid (MA+PGA) were 4.4 mmol/liter (after workshift) and 2.1 mmol/liter (next morning), respectively. Multivariate analysis of covariance on log-transformed GPA Vf data with models allowing adjustment for age, gender, smoking status, and styrene exposure showed that N/N Vf were nearly significantly increased among all of the exposed workers (adjusted geometric mean, 6.3 per million versus 5.0 in the controls; P = 0.058) and were statistically significantly elevated (adjusted geometric mean, 6.8 versus 5.0 in the controls; P = 0.036) among workers classified into a high-exposure group according to personal TWA8-h concentration of styrene in the breathing zone of > or = 85 mg/m3 (20 ppm; Finnish threshold limit value). Women in this high exposure group showed especially elevated N/N Vf (adjusted geometric mean 8.5 versus 5.3 in control women; P = 0.020); this elevation was also significant if urinary MA+PGA of > or = 1.2 mmol/liter was used as the basis of classification (adjusted geometric mean, 8.3; P = 0.030). The occupational exposure could not be shown to influence phi/N Vf. Cigarette smoking was associated with significantly elevated GPA Vf among active smokers (P = 0.042 for phi/N and P = 0.020 for N/N) and among active and ex-smokers combined (P = 0.014 for N/N). Its influence on phi/N Vf was especially clear among active smokers in the control group (P = 0.005). An effect of smoking, nearly statistically significant, was also observed for the phi/N Vf of control ex-smokers (P = 0.055) and of all active and ex-smokers combined (P = 0.050). Thus, the two characterized chemical exposures experienced by this group of workers and controls appear to produce differential effects on the two independent classes of GPA variants enumerated in the assay. This result suggests that the genotoxicity of these agents is mediated, at least in part, by different genetic mechanisms. Styrene exposure is associated with a specific increase in GPA N/N Vf; these allele loss and duplication variants reflect predominantly somatic recombination mechanisms in erythroid progenitor cells. Tobacco smoke exposure in active and ex-smokers is also associated not only with an increase in N/N Vf but also with an increase in phi/N Vf, reflecting the induction of GPA gene-inactivating mutations, including point mutations and deletions. This finding is consistent with a broad mechanistic spectrum of tobacco smoke genotoxicity associated with this complex mixture of chemical mutagens. Finally, there was no detectable effect of age on phi/N Vf; however, a highly significant (P = 0.0002) increase in N/N Vf with age, even after adjustment for other variables, was observed.


General Self-Efficacy and Mortality in the USA; Racial Differences.
General self-efficacy has been historically assumed to have universal health implications. However, less is known about population differences in long-term health effects of general self-efficacy across diverse populations. This study compared black and white American adults for (1) the association between psychosocial and health factors and general self-efficacy at baseline, and (2) the association between baseline self-efficacy and long-term risk of all-cause mortality over 25 years. The Americans' Changing Lives (ACL) study, 1986-2011, is a nationally representative longitudinal cohort of US adults. The study followed 3361 black (n = 1156) and white (n = 2205) adults for up to 25 years. General self-efficacy as well as demographics, socioeconomics, stressful life events, health behaviors, obesity, depressive symptoms, and self-rated health were measured at baseline in 1986. The outcome was time to all-cause mortality since 1986. Race was the focal moderator. Logistic regression and proportional hazards models were used for data analysis. Although blacks had lower general self-efficacy, this association was fully explained by socioeconomic factors (education and income). Our logistic regression suggested interactions between race and education, self-rated health, and stress on general self-efficacy at baseline. Baseline general self-efficacy was associated with risk of mortality in the pooled sample. Race interacted with baseline general self-efficacy on mortality risk, suggesting stronger association for whites than blacks. Black-white differences exist in psychosocial and health factors associated with self-efficacy in the USA. Low general self-efficacy does not increase mortality risk for blacks. Future research should test whether socioeconomic status, race-related attitudes, world views, attributions, and locus of control can potentially explain why low self-efficacy is not associated with higher risk of mortality among American blacks.


Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype.
Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using 3109 Caucasian samples in 745 families, we evaluated association in the overall dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS genes were tested for genetic association with NTD subtypes, both for main effects as well as for the presence of interactions with the MTHFR C677T polymorphism. Nominal main effect associations were found with all subtypes, across all three NOS genes, and interactions were observed between SNPs in all three NOS genes and MTHFR C677T. Unlike the previous report, the most significant associations in our dataset were with cranial subtypes and the AG genotype of rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous findings by implicating a role for all three NOS genes, independently and through interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes.


The impact of a temporary medical ward closure on emergency department and hospital service delivery outcomes.
To describe the effect of a 3-week closure of a 28-bed medical ward on Emergency Department (ED) and hospital outcomes. This was a prospective comparative observational study of all ED attendances (visits; n = 11 383) made to a regional teaching hospital in Queensland, Australia, during a 9-week period (November 24, 2008-January 4, 2009). A 3-week period of ward closure was compared with equal time periods before and after. Hospital health information systems data were linked manually to describe and compare outcomes: median ED length of stay, access block, hospital length of stay, and in-hospital mortality. Ward closure reduced hospital bed capacity by 5.9%. During ward closure there was a higher proportion of access block (38% vs 33% in both pre- and posttimes), longer wait time to see a doctor, and longer overall ED length of stay, compared with pre-ward closure time period. Temporarily closing a medical ward had a negative effect on some ED and hospital outcomes. When major refurbishments are required, alternative capacity measures need to be considered to minimize the impact on health service delivery and patient outcomes. Reducing elective surgery and opening replacement beds elsewhere in the hospital are possible solutions.


Hepatoid carcinoma of the pancreas combined with neuroendocrine carcinoma.
Hepatoid carcinoma is a primary extrahepatic carcinoma whose morphology, immunohistochemistry, and behavior are similar to those of hepatocellular carcinoma. The most common sites of extrahepatic carcinoma are the stomach and ovary, but nine cases of hepatocellular differentiation of the pancreas have been reported in the literature. We report another case of hepatoid carcinoma of the pancreas that was associated with the development of a pancreatic endocrine carcinoma in a 46-year-old man. Serum alpha-fetoprotein (AFP) was elevated to 262.49 IU/mL and radiological examinations revealed a mass measuring 7.5 cm in diameter in the head of the pancreas. He underwent a conventional Whipple operation, and light microscopy showed adenocarcinoma that was immunopositive for AFP, hepatocyte antigen, cytokeratin, chromogranin, synaptophysin, and alpha-1 antichymotrypsin. Although hepatoid differentiation was not shown unequivocally histologically, other immunohistochemistry findings supported the diagnosis of hepatoid carcinoma combined with neuroendocrine carcinoma. The patient was healthy and had no evidence of recurrence at 4 months after the surgery. This report describes why hepatoid carcinoma should be considered as a differential diagnosis of a pancreatic mass, especially when serum AFP is elevated.


Ellagitannin from Quercus infectoria eradicates intestinal colonization and prevents renal injuries in mice infected with Escherichia coli O157 : H7.
The use of antimicrobial agents in the management of patients infected with Shiga toxin-producing Escherichia coli (STEC) O157 : H7 remains controversial. Here, we examined the antibacterial efficacy of a natural product, ellagitannin from Quercus infectoria (Qi 4), against the organism in a murine model. Streptomycin-pretreated mice were orogastrically inoculated with 2×10(9) c.f.u. streptomycin-resistant E. coli O157 : H7. The results demonstrated a stable high level of STEC present in the faeces of the infected animals. The bacterial levels in infected mice receiving Qi 4 at MIC and 2×MIC were not significantly different from those of the untreated group (t-test; P>0.05). In contrast, Qi 4 at 4×MIC significantly reduced the numbers of STEC within 2 days (t-test; 0.05>P>0.01). No viable bacteria were detected between day 5 and day 10. Similarly, at day 10, no organisms were detected from the intestines of the Qi 4-treated group, while they were recovered at levels of 10(8-11) and 10(5-10) c.f.u. g(-1) in the colons and caeca of the infected mice, respectively. Histopathological findings from the infected kidneys revealed a marked increase in the number of mesangial cells and mesangial matrix. Ultrastructural examination of the kidneys from the infected mice also demonstrated proliferation of mesangial cells and an increase in the mesangial matrix. Cellular injury of endothelial cells with irregular borders and cytoplasmic bleb formation were noted. In contrast, the effects were not observed in the animals treated with Qi 4. The results clearly indicated that administration of Qi 4 could effectively eradicate the colonization of STEC O157 : H7 in the intestinal tract of mice and prevent renal injury. This compound may be an alternative candidate for a therapeutic agent against infections caused by this dangerous organism.


Associations between physical activity and the neighbourhood social environment: baseline results from the HABITAT multilevel study.
Limitations have arisen when measuring associations between the neighbourhood social environment and physical activity, including same-source bias, and the reliability of aggregated neighbourhood-level social environment measures. This study examines cross-sectional associations between the neighbourhood social environment (perceptions of incivilities, crime, and social cohesion) and self-reported physical activity, while accounting for same-source bias and reliability of neighbourhood-level exposure measures, using data from a large population-based clustered sample. This investigation included 11,035 residents aged 40-65years from 200 neighbourhoods in Brisbane, Australia, in 2007. Respondents self-reported their physical activity and perceptions of the social environment (neighbourhood incivilities, crime and safety, and social cohesion). Models were adjusted for individual-level education, occupation, and household income, and neighbourhood disadvantage. Exposure measures were generated via split clusters and an empirical Bayes estimation procedure. Data were analysed in 2016 using multilevel multinomial logistic regression. Residents of neighbourhoods with the highest incivilities and crime, and lowest social cohesion were reference categories. Individuals were more likely to be in the higher physical activity categories if they were in neighbourhoods with the lowest incivilities and the lowest crime. No associations were found between social cohesion and physical activity. This study provides a basis from which to gain a clearer understanding of the relationship between the neighbourhood social environment and individual physical activity. Further work is required to explore the pathways between perceptions of the neighbourhood social environment and physical activity.


The physical therapy prescription.
Numerous guidelines recommend physical therapy for the management of musculoskeletal conditions. However, specific recommendations are lacking concerning which exercises and adjunct modalities to use. Physical therapists use various techniques to reduce pain and improve mobility and flexibility. There is some evidence that specific exercises performed with the instruction of physical therapists improve outcomes in patients with low back pain. For most modalities, evidence of effectiveness is variable and controlled trials are lacking. Multiple modalities may be used to treat one clinical condition; decisions for the treatment of an individual patient depend on the expertise of the therapist, the equipment available, and the desire of the attending physician. A physical therapy prescription should include the diagnosis; type, frequency, and duration of the prescribed therapy; goals of therapy; and safety precautions.


Modification of Sialic Acids on Solid Phase: Accurate Characterization of Protein Sialylation.
Sialic acids play many important roles in several physiological and pathological processes, including cancers, infection, and blood diseases. Sialic acids are fragile and prone to fragmentation under electrospray ionization and matrix-assisted laser desorption/ionization. It is crucial to modify sialic acids for qualitative and quantitative identification of their change in abundance in complex biological samples. Permethylation is a method of choice for sialic acid stabilization, but the harsh conditions during permethylation may lead to the decomposition of O-acetyl groups. Esterification or amidation in solution effectively protects sialic acids, yet it is not trivial to purify glycans from their reagents. Quantitative analysis of glycans can be achieved by labeling their reducing end using fluorescent tags. Loss of sialic acids during labeling is a major concern. In this study, we demonstrated the utility of sialic acids modification for the analysis of sialyl oligosaccharides and glycopeptides. Without modification, sialic acids are partially or completely lost during sample preparation, leading to the presence of false glycans or glycopeptides in the sample. The stabilized sialic acids not only result in accurate identification of sialylated glycans but also improve the characterization of intact glycopeptides. The modification of sialic acids on the solid support facilitates analysis of glycans and their intact glycoproteins.


Assessment of intestinal availability (FG) of substrate drugs of cytochrome p450s by analyzing changes in pharmacokinetic properties caused by drug-drug interactions.
In this study, we developed the drug-drug interaction (DDI) method as a new assessment technique of intestinal availability (F(G), the fraction of drug transferred from the intestinal enterocytes into the liver, escaping from intestinal metabolism) based on the clearance theory. This method evaluates F(G) from changes caused by DDIs in the area under the blood concentration-time curve and in the elimination half-life of victim drugs. Application of the DDI method to data from the literature revealed that the mean and S.D. of F(G) values for 20 substrate drugs of CYP3A was 0.56 ± 0.29, whereas that for 8 substrate drugs of CYP2C9, CYP2C19, and CYP2D6 was 0.86 ± 0.11. These results were consistent with the fact that intestinal metabolism is mediated predominantly by CYP3A. The DDI method showed reasonable correlations with the conventional i.v./p.o. method and the grape fruit juice (GFJ) method (coefficients of determination of 0.41 and 0.81, respectively). The i.v./p.o. method was more susceptible to fluctuations in the hepatic blood flow rate compared with the DDI and GFJ methods. The DDI method evaluates F(G) separating from the absorption ratio (F(A)) although it requires approximation of F(A). Since preciseness of approximation of F(A) does not greatly affect the evaluation of F(G) by the DDI method, we proposed a reasonable approximation method of F(A) for the evaluation of F(G) in the DDI method. The DDI method would be applicable to a broad range of situations in which various DDI data are utilizable.


Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product.
Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo.


The revolution that wasn't: a new interpretation of the origin of modern human behavior.
Proponents of the model known as the "human revolution" claim that modern human behaviors arose suddenly, and nearly simultaneously, throughout the Old World ca. 40-50 ka. This fundamental behavioral shift is purported to signal a cognitive advance, a possible reorganization of the brain, and the origin of language. Because the earliest modern human fossils, Homo sapiens sensu stricto, are found in Africa and the adjacent region of the Levant at >100 ka, the "human revolution" model creates a time lag between the appearance of anatomical modernity and perceived behavioral modernity, and creates the impression that the earliest modern Africans were behaviorally primitive. This view of events stems from a profound Eurocentric bias and a failure to appreciate the depth and breadth of the African archaeological record. In fact, many of the components of the "human revolution" claimed to appear at 40-50 ka are found in the African Middle Stone Age tens of thousands of years earlier. These features include blade and microlithic technology, bone tools, increased geographic range, specialized hunting, the use of aquatic resources, long distance trade, systematic processing and use of pigment, and art and decoration. These items do not occur suddenly together as predicted by the "human revolution" model, but at sites that are widely separated in space and time. This suggests a gradual assembling of the package of modern human behaviors in Africa, and its later export to other regions of the Old World. The African Middle and early Late Pleistocene hominid fossil record is fairly continuous and in it can be recognized a number of probably distinct species that provide plausible ancestors for H. sapiens. The appearance of Middle Stone Age technology and the first signs of modern behavior coincide with the appearance of fossils that have been attributed to H. helmei, suggesting the behavior of H. helmei is distinct from that of earlier hominid species and quite similar to that of modern people. If on anatomical and behavioral grounds H. helmei is sunk into H. sapiens, the origin of our species is linked with the appearance of Middle Stone Age technology at 250-300 ka.


Vitamin D and the immune system: role in protection against bacterial infection.
The role of vitamin D extends well beyond that of regulating calcium homeostasis. One of these areas is immune function. Immunity is both adaptive and innate, and vitamin D signaling is operative in both. This review will examine these actions of vitamin D, in particular the role of vitamin D in host defense against infection. This review will consider two examples of vitamin D-regulated innate immunity that have been recently explored: the role of vitamin D signaling within macrophages to enable them to respond to and kill Mycobacterium tuberculosis organisms, and the role of vitamin D signaling in the keratinocytes of the epidermis to enable them to respond to disruption of their barrier function. Potential application to periodontal disease will then be considered. Both adaptive and innate immune processes are two edged: beneficial and harmful. Although suppression of adaptive immunity may be beneficial in a number of self-destructive diseases, such suppression may predispose to infection. Enhancement of innate immunity is clearly beneficial in diseases like tuberculosis, but potentiation of proinflammatory processes can increase tissue destruction as in bone loss in periodontal disease. The balance, however, favors adequate vitamin D nutrition in host defense against infection.


Reconfiguration of the achene and receptacle metabolic networks during strawberry fruit development.
The anatomy of strawberry (Fragaria x ananassa) fruit, in which the achene is found on the outer part of the fruit, makes it an excellent species for studying the regulation of fruit development. It can provide a model for the cross talk between primary and secondary metabolism, whose role is of pivotal importance in the process. By combining gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry with the aim of addressing the metabolic regulation underlying fruit seed development, we simultaneously analyzed the composition of primary and secondary metabolites, separately, in achene and receptacle during fruit ripening of strawberry cultivar Herut. The results from these analyses suggest that changes in primary and secondary metabolism reflect organ and developmental specificities. For instance, the receptacle was characterized by increases in sugars and their direct derivatives, while the achene was characterized by a major decrease in the levels of carbon- and nitrogen-rich compounds, with the exception of storage-related metabolites (e.g. raffinose). Furthermore, the receptacle, and to a lesser extent the achene, exhibited dynamic fluctuations in the levels and nature of secondary metabolites across the ripening process. In the receptacle, proanthocyanidins and flavonol derivatives characterized mainly early developmental stages, while anthocyanins were abundant in the mature red stage; in the achene, ellagitannin and flavonoids were abundant during early and late development, respectively. Correlation-based network analysis suggested that metabolism is substantially coordinated during early development in either organ. Nonetheless, a higher degree of connectivity within and between metabolic pathways was measured in the achenes. The data are discussed within the context of current models both of the interaction of primary and secondary metabolism and of the metabolic interaction between the different plant organs.


Efficacy and acceptance of a high-velocity microdroplet device for interdental cleaning in gingivitis patients-A monitored, randomized controlled trial.
To compare in a randomized clinical trial the efficacy of a high-velocity microdroplet device for interdental cleaning vs dental floss at reducing plaque and gingivitis. Sixty participants with an irregular interdental home cleaning regime were randomly assigned to use either a microdroplet device (n=40, test) or dental floss (n=20, control) for 4 weeks. At baseline and reassessment, the papilla bleeding index, the modified proximal plaque index and the amount of gingival crevicular fluid (GCF) were recorded. At the second appointment, participants completed a questionnaire regarding their assigned interdental cleaning option. The process quality of this investigator-initiated trial was ensured by independent scientific observers and media representatives. Improvement in the interdental cleaning routine reduced gingivitis in both groups (P<.05). The microdroplet device was more effective at reducing plaque (P=.003). The GCF amount remained the same in both groups. Comfort of use was greater with the microdroplet device. However, self-reported effectiveness was superior with dental floss. About 85% of participants using the microdroplet device said they would continue daily use. Improving the interdental cleaning routine with the microdroplet device or dental floss reduced gingivitis and plaque in both groups. Acceptance regarding comfort of use was higher with the microdroplet device. Dental floss remained the first choice for narrow interdental spaces, yet the microdroplet device offers an effective and well-accepted alternative for patients who fail the proper flossing routine.


Cloning and molecular characterization of telomerase reverse transcriptase (TERT) and telomere length analysis of Peromyscus leucopus.
Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase complex that regulates telomerase activity to maintain telomere length for all animals with linear chromosomes. As the Mus musculus (MM) laboratory mouse has very long telomeres compared to humans, a potential alternative animal model for telomere research is the Peromyscus leucopus (PL) mouse that has telomere lengths close to the human range and has the wild counterparts for comparison. We report the full TERT coding sequence (pTERT) from PL mice to use in the telomere research. Comparative analysis with eight other mammalian TERTs revealed a pTERT protein considerably homologous to other TERTs and preserved all TERT specific-sequence signatures, yet with some distinctive features. pTERT displayed the highest nucleotide and amino acid sequence homology with hamster TERT. Unlike human but similar to MM mice, pTERT expression was detected in various adult somatic tissues of PL mice, with the highest expression in testes. Four different captive stocks of PL mice and wild-captured PL mice each displayed group-specific average telomere lengths, with the longest and shortest telomeres in inbred and outbred stock mice, respectively. pTERT showed considerable numbers of synonymous and nonsynonymous mutations. A pTERT proximal promoter region cloned was homologous among PL and MM mice and rat, but with species-specific features. From PL mice, we further cloned and characterized ribosomal protein, large, P0 (pRPLP0) to use as an internal control for various assays. Peromyscus mice have been extensively used for various studies, including human diseases, for which pTERT and pRPLP0 would be useful tools.


The host endocytic pathway is essential for Plasmodium berghei late liver stage development.
The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in the parasite life cycle and remains a promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes and achieve one of the fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about the parasite interactions with the host hepatocyte. Using immunofluorescence, live cell imaging and electron microscopy, we show that Plasmodium berghei parasites are surrounded by vesicles from the host late endocytic pathway. We found that these vesicles are acidic and contain the membrane markers Rab7a, CD63 and LAMP1. When host cell vesicle acidification was disrupted using ammonium chloride or Concanamycin A during the late liver stage of infection, parasite survival was not affected, but schizont size was significantly decreased. Furthermore, when the host cell endocytic pathway was loaded with BSA-gold, gold particles were found within the parasite cytoplasm, showing the transport of material from the host endocytic pathway toward the parasite interior. These observations reveal a novel Plasmodium-host interaction and suggest that vesicles from the host endolysosomal pathway could represent an important source of nutrients exploited by the fast-growing late liver stage parasites.


Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand.
The therapy of Plasmodium falciparum malaria continues to be a problem in many parts of Southeast Asia because of multidrug resistance to nearly all existing antimalarial drugs. Atovaquone is a novel hydroxynaphthoquinone with broad spectrum anti-protozoal activity. We recently evaluated the antimalarial activity of atovaquone in a series of dose-ranging studies in 317 patients with malaria at the Bangkok Hospital for Tropical Diseases. Originally, the drug was administered alone. Using atovaquone alone resulted in satisfactory, initial clinical responses in all patients; the mean parasite and fever clearance times were 62 and 53 hr, respectively. However, irrespective of the duration of therapy, overall cure rates were approximately 67%. In vitro sensitivity studies on parasites taken from patients prior to treatment and at the time of recrudescence showed a marked decrease in susceptibility to atovaquone in the recrudescent parasites. To improve cure rates, atovaquone was administered in combination with other drugs with antimalarial activity. Proguanil and tetracycline were chosen due to laboratory evidence of potentiation; doxycycline was selected because it has a longer half-life than tetracycline. Although pyrimethamine did not show laboratory evidence of potentiation with atovaquone, it was chosen as an alternative inhibitor of dihydrofolic acid reductase with a longer half-life than proguanil. The clinical studies with these drug combinations confirmed the laboratory results with marked improvement in cure rates for proguanil, tetracycline, and doxycycline; pyrimethamine showed only minimal improvement. Proguanil was subsequently selected as the preferred drug partner because of its long record of safety and the ability to use the drug in pregnant women and children. Of the 104 patients with falciparum malaria treated with atovaquone plus proguanil for 3-7 days, 101 were cured and had virtually no adverse side effects. The combination of atovaquone and proguanil also was effective in eliminating erythrocytic forms of P. vivax, but parasitemia recurred in most patients.


DNA polymerase eta is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse.
Mutations at A/T bases within immunoglobulin genes have been shown to be generated by a repair pathway involving the DNA-binding moiety of the mismatch repair complex constituted by the MSH2-MSH6 proteins, together with DNA polymerase eta (pol eta). However, residual A/T mutagenesis is still observed upon inactivation in the mouse of each of these factors, suggesting that the panel of activities involved might be more complex. We reported previously (Delbos, F., A. De Smet, A. Faili, S. Aoufouchi, J.-C. Weill, and C.-A. Reynaud. 2005. J. Exp. Med. 201:1191-1196) that residual A/T mutagenesis in pol eta-deficient mice was likely contributed by another enzyme not normally involved in hypermutation, DNA polymerase kappa, which is mobilized in the absence of the normal polymerase partner. We report the complete absence of A/T mutations in MSH2-pol eta double-deficient mice, thus indicating that the residual A/T mutagenesis in MSH2-deficient mice is contributed by pol eta, now recruited by uracil N-glycosylase, the second DNA repair pathway involved in hypermutation. We propose that this particular recruitment of pol eta corresponds to a profound modification of the function of uracil glycosylase in the absence of the mismatch repair complex, suggesting that MSH2-MSH6 actively prevent uracil glycosylase from error-free repair during hypermutation. pol eta thus appears to be the sole contributor of A/T mutations in the normal physiological context.


Meta-analysis of adiponectin polymorphisms and colorectal cancer risk.
The adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk. All eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model. A total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American. This meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.


Black and green tea - luminol false-negative bloodstains detection.
The antioxidant properties of black and green teas are well known. It is also possible to determine their antioxidant capacity by using a chemiluminscent method. This method is based on the measurement of the delay in the emission of light from the luminol reaction in the presence of the antioxidant. Bloodstains which are invisible to the naked eye can also be detected by luminol. Three common methods (detection using the Grodsky or Weber formulations and by Bluestar® Forensic latent bloodstain reagent) are based on the luminol chemiluminescence reaction. The bloodstains can be masked by drinks and/or foods containing antioxidants. The aim of this work was to compare the ability of black and green teas containing antioxidants to cause false negative results during chemiluminescent bloodstain detection.


Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies.
Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) can alter ventricular myocyte calcium handling, these fatty acids could adversely affect cardiac contractile function, particularly following myocardial infarction. Therefore, 4 wk after myocardial infarction, dogs were randomly assigned to either placebo (corn oil, 1 g/day, n = 16) or n-3 PUFAs supplement [docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) ethyl esters; 1, 2, or 4 g/day; n = 7, 8, and 12, respectively] groups. In vivo, ventricular function was evaluated by echocardiography before and after 3 mo of treatment. At the end of the 3-mo period, hearts were removed and in vitro function was evaluated using right ventricular trabeculae and isolated left ventricular myocytes. The treatment elicited significant (P < 0.0001) dose-dependent increases (16.4-fold increase with 4 g/day) in left ventricular tissue and red blood cell n-3 PUFA levels (EPA + DHA, placebo, 0.42 +/- 0.04; 1 g/day, 3.02 +/- 0.23; 2 g/day, 3.63 +/- 0.17; and 4 g/day, 6.97 +/- 0.33%). Regardless of the dose, n-3 PUFA treatment did not alter ventricular function in the intact animal (e.g., 4 g/day, fractional shortening: pre, 42.9 +/- 1.6 vs. post, 40.1 +/- 1.7%; placebo: pre, 39.2 +/- 1.3 vs. post, 38.4 +/- 1.6%). The developed force per cross-sectional area, changes in length- and frequency-dependent behavior in contractile force, and the inotropic response to beta-adrenoceptor activation were also similar for trabeculae obtained from placebo- or n-3 PUFA-treated dogs. Finally, calcium currents and calcium transients were the same in myocytes from n-3 PUFA- and placebo-treated dogs. Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions.


Quality of medical devices and in vitro diagnostics in resource-limited settings.
The phenomenon of poor-quality medicines in resource-limited settings is well documented, and field observations reveal similar problems with medical devices (MDs) and in vitro diagnostics (IVDs). In scientific literature, however, there are only scarce reports and documents providing evidence of quality problems of MDs or IVDs in resource-limited settings. This discrepancy may be ascribed to (i) the poor regulatory oversight of MDs/IVDs in resource-limited settings, (ii) a general lack of awareness of the problem of poor-quality MDs/IVDs amongst the scientific community and decision-makers, and (iii) poor quality assurance in diagnostic laboratories in resource-poor settings, precluding tracing quality problems of IVDs from the other potential causes of diagnostic inaccuracy. The problem of poor-quality MDs/IVDs in resource-limited settings is a complex one to address. Firstly, operational definitions for substandard and counterfeit MDs/IVDs are required, as well as ad hoc field surveys, to ensure proper appraisal of the real extent of the problem. Investments are needed to reinforce the national regulatory oversights on MDs/IVDs in resource-limited settings, and to encourage a proactive and transparent exchange of information between Northern and Southern regulatory authorities. Industrialized countries can play a role by expanding and strengthening their regulatory oversight and quality labels to those MDs/IVDs that are frequently used in resource-poor settings. Hopefully, the combination of these measures will result in better protection of patients in resource-poor countries from the effects of being exposed to poor-quality MDs and IVDs.


A cross-sectional observational study of healthcare professional views of factors affecting teenage adherence with antipsychotic medication.
Delays in effective treatment of a first episode psychosis can result in more severe symptoms, a longer time to achieve symptom control and a poorer quality of life; yet around 40% do not take antipsychotic medication as prescribed. There is evidence that patients and staff have different perceptions of what affects adherence with medication. Research in adults suggests healthcare professionals and patients understand the importance of good insight in promoting adherence with medication for schizophrenia; however, healthcare staff may overestimate the impact of side effects and underestimate the importance of medication effectiveness. There is also some evidence to suggest that motivations to take prescribed medication may differ in first and multi-episode psychosis. This research therefore sought views of staff working with adolescents diagnosed with first episode psychosis about what factors affected adherence with antipsychotic medication. Staff responding to the survey felt that young people were more likely to take medication if they felt it would make them better, prevent relapse and if they had a positive rapport with staff. As in an adult population, side effects, particularly weight gain, sedation and muscular side effects, were expressed as a common reason for poor adherence. Doctors and nurses assigned differing importance to parameters such as family views of medication, fear of admission and a preference for cannabis over medication suggesting that views may differ between professional groups Views of young people will be obtained in the next phase of the research study to enable comparison with staff views and consideration of staff interventions to better promote medication adherence. Antipsychotic medication is an effective treatment for first episode psychosis; yet 40% of patients do not take medication as prescribed. Previous research in adults with schizophrenia comparing healthcare professional and patient views suggests that while healthcare professionals recognize the importance of insight in promoting medication adherence, they underestimate the importance of medication efficacy and overestimate the impact of side effects. It was hypothesized that staff in this study would also recognize the importance of insight and positive medication attitudes in teenagers with psychosis, but overestimate the impact of side effects on medication adherence. This cross-sectional observational study sought staff views about factors affecting antipsychotic medication adherence in those aged between 14 and 18 years. An online survey was distributed and 60 responses were subsequently returned. Staff felt that good medication insight as well as positive relationships with staff were important determinants of good medication adherence. The most important influences of poor adherence were poor insight, side effects of medication and a wish to exert personal control around medication decisions. The results therefore confirmed the initial hypothesis. Published literature also provides support for some, but not all, of the staff views expressed in survey responses.


Complex spatiotemporal phenological shifts as a response to rainfall changes.
• Climatic warming produces significant gradual alterations in the timing of life-cycle events, and here we study the phenological effects of rainfall-pattern changes. • We conducted ecosystem field experiments that partially excluded rain and runoff during the growing season in a Mediterranean forest and in a mediterranean shrubland. Studies of time-series of leaf-unfolding, flowering and fruiting over the last 50 yr in central Catalonia were carried out, and greenup onset in the Iberian Peninsula was monitored by satellite images. • Experimental, historical and geographical changes in rainfall produced significant, complex and strongly species-specific, as well as spatially and temporally variable, phenological effects. Among these changes, it was found that in the Iberian Peninsula, greenup onset changes from spring (triggered by rising temperatures) in the northern cool-wet regions to autumn (triggered by the arrival of autumn rainfalls) in the southern warm-dry regions. Even in the mesic Mediterranean central Catalonia (NE of the peninsula) rainfall had a stronger relative influence than temperature on fruiting phenology. • The results show that changes in rainfall and water availability, an important driver of climate change, can cause complex phenological changes with likely far-reaching consequences for ecosystem and biosphere functioning and structure. The seasonal shift in the Iberian Peninsula further highlights this importance and indicates that vegetation may respond to climate change not only with gradual, but also with abrupt temporal and spatial, changes in the timing of greenup onset.


Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes.
The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of α-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.


Triggering TLR2, -3, -4, -5, and -8 reinforces the restrictive nature of M1- and M2-polarized macrophages to HIV.
Macrophages must react to a large number of pathogens and their effects. In chronic HIV infection, the microenvironment changes with an influx of microbial products that trigger Toll-like receptors (TLRs). That dynamic nature can be replicated ex vivo by the proinflammatory (M1-polarized) and alternatively activated (M2-polarized) macrophages. Thus, we determined how polarized macrophages primed by various TLR agonists support HIV replication. Triggering of TLR2, -3, -4, -5, and -8 reinforced the low level of permissiveness in polarized macrophages. HIV was inhibited even more in M1-polarized macrophages than in macrophages activated only by TLR agonists. HIV was inhibited before its integration into the host chromosome. Polarization and triggering by various TLR agonists resulted in distinct cytokine profiles, endocytic activity, and distinct upregulation of restriction factors of HIV. Thus, different mechanisms likely contribute to the HIV-inhibitory effects. In chronic HIV infection, macrophages might become less permissive to HIV due to changes in the microenvironment. The high level of reactivity of polarized macrophages to TLR triggering may be exploited for immunotherapeutic strategies. Macrophages are a major target of HIV-1 infection. Different cell types in this very heterogeneous cell population respond differently to stimuli. In vitro, the heterogeneity is mimicked by their polarization into proinflammatory and alternatively activated macrophages. Here we explored the extent to which agonists triggering the TLR family affect HIV replication in polarized macrophages. We found that a number of TLR agonists blocked HIV replication substantially when given before infection. We also report the mechanisms of how TLR agonists exert their inhibitory action. Our findings may advance our understanding of which and how TLR agonists block HIV infection in polarized macrophages and may facilitate the design of novel immunotherapeutic approaches.


Can we, should we, eradicate the meningococcus?
The eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. The introduction of vaccines against Neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. The limited number of meningococcal serogroups, lack of an animal reservoir, and importance of meningococcal disease are considerations in favour of eradication; however, the commensal nature of most infections, the high diversity of meningococcal populations, and the lack of comprehensive vaccines are all factors that suggest that this is not feasible. Indeed, any such attempt might be harmful by perturbing the human microbiome and its interaction with the immune system. On balance, the control and possible elimination of disease caused by particular disease-associated meningococcal genotypes is a more achievable and worthwhile goal.


A multi-scale perspective of water pulses in dryland ecosystems: climatology and ecohydrology of the western USA.
In dryland ecosystems, the timing and magnitude of precipitation pulses drive many key ecological processes, notably soil water availability for plants and soil microbiota. Plant available water has frequently been viewed simply as incoming precipitation, yet processes at larger scales drive precipitation pulses, and the subsequent transformation of precipitation pulses to plant available water are complex. We provide an overview of the factors that influence the spatial and temporal availability of water to plants and soil biota using examples from western USA drylands. Large spatial- and temporal-scale drivers of regional precipitation patterns include the position of the jet streams and frontal boundaries, the North American Monsoon, El Niño Southern Oscillation events, and the Pacific Decadal Oscillation. Topography and orography modify the patterns set up by the larger-scale drivers, resulting in regional patterns (10(2)-10(6) km2) of precipitation magnitude, timing, and variation. Together, the large-scale and regional drivers impose important pulsed patterns on long-term precipitation trends at landscape scales, in which most site precipitation is received as small events (< 5 mm) and with most of the intervals between events being short (< 10 days). The drivers also influence the translation of precipitation events into available water via linkages between soil water content and components of the water budget, including interception, infiltration and runoff, soil evaporation, plant water use and hydraulic redistribution, and seepage below the rooting zone. Soil water content varies not only vertically with depth but also horizontally beneath versus between plants and/or soil crusts in ways that are ecologically important to different plant and crust types. We highlight the importance of considering larger-scale drivers, and their effects on regional patterns; small, frequent precipitation events; and spatio-temporal heterogeneity in soil water content in translating from climatology to precipitation pulses to the dryland ecohydrology of water availability for plants and soil biota.


Kinetic and training comparisons between assisted, resisted, and free countermovement jumps.
Elastic band assisted and resisted jump training may be a novel way to develop lower-body power. The purpose of this investigation was to (a) determine the kinetic differences between assisted, free, and resisted countermovement jumps and (b), investigate the effects of contrast training using either assisted, free, or resisted countermovement jump training on vertical jump performance in well-trained athletes. In part 1, 8 recreationally trained men were assessed for force output, relative peak power (PP·kg(-1)) and peak velocity during the 3 types of jump. The highest peak force was achieved in the resisted jump method, while PP·kg(-1) and peak velocity were greatest in the assisted jump. Each type of jump produced a different pattern of maximal values of the variables measured, which may have implications for developing separate components of muscular power. In part 2, 28 professional rugby players were assessed for vertical jump height before and after 4 weeks of either assisted (n = 9), resisted (n = 11), or free (n = 8) countermovement jump training. Relative to changes in the control group (1.3 ± 9.2%, mean ± SD), there were clear small improvements in jump height in the assisted (6.7 ± 9.6%) and the resisted jump training group (4.0 ± 8.8%). Elastic band assisted and resisted jump training are both effective methods for improving jump height and can be easily implemented into current training programs via contrast training methods or as a part of plyometric training sessions. Assisted and resisted jump training is recommended for athletes in whom explosive lower-body movements such as jumping and sprinting are performed as part of competition.


Couple relationship education: A randomized controlled trial of professional contact and self-directed tools.
The aim of this randomized controlled trial was to examine the efficacy of an evidence-based relationship distress prevention program, the Couples Coping Enhancement Training (CCET), in dual well-earning couples and to investigate whether effects vary by (a) hours of professional contact and (b) mode of delivery (face to face vs. self-learning DVD). N = 159 couples were randomly assigned to 1 of 4 intervention conditions: (1) standard CCET (15 hours face to face), (2) compact CCET (12 hr face to face), (3) short CCET (self-learning DVD + 8 hr face to face), or (4) wait-list control group. Relationship satisfaction and dyadic coping skills were assessed by means of questionnaires completed prior to and 2 weeks after completion of the treatment, at 3-month follow-up, and at 6-month follow-up. Baseline latent change models for 2 factors showed that the CCET enhanced relationship satisfaction and dyadic coping skills in couples relative to the wait-list control group, albeit effects were small. The standard format of the CCET was not more effective than the compact or the short format indicating that reduced amount of professional contact did not decrease the treatment's efficacy and that the self-learning DVD successfully replaced the psycho-educational part of the program. Since dual earner couples usually face multiple stressors, it is a promising finding that they can strengthen their relationship with a relatively short time investment. (PsycINFO Database Record


Predictable modulation of cancer treatment outcomes by the gut microbiota.
The gut microbiota has the potential to influence the efficacy of cancer therapy. Here, we investigated the contribution of the intestinal microbiome on treatment outcomes in a heterogeneous cohort that included multiple cancer types to identify microbes with a global impact on immune response. Human gut metagenomic analysis revealed that responder patients had significantly higher microbial diversity and different microbiota compositions compared to non-responders. A machine-learning model was developed and validated in an independent cohort to predict treatment outcomes based on gut microbiota composition and functional repertoires of responders and non-responders. Specific species, Bacteroides ovatus and Bacteroides xylanisolvens, were positively correlated with treatment outcomes. Oral gavage of these responder bacteria significantly increased the efficacy of erlotinib and induced the expression of CXCL9 and IFN-γ in a murine lung cancer model. These data suggest a predictable impact of specific constituents of the microbiota on tumor growth and cancer treatment outcomes with implications for both prognosis and therapy.