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Despite over 80 years of clinical experience with coagulation factor (F)VIII inhibitors, surprisingly little is known about the in vivo mechanism of this most serious complication of replacement therapy for hemophilia A. These neutralizing anti-drug alloantibodies arise in ~30% of patients. Inhibitor formation is T cell-dependent, but events leading up to helper T cell activation have been elusive due in part to the complex anatomy and cellular makeup of the spleen. Here, we show that FVIII antigen presentation to CD4+ T cells critically depends on a select set of several anatomically distinct antigen presenting cells, whereby marginal zone B cells, marginal zone and marginal metallophilic but not red pulp macrophages (RPMFs) participate in shuttling FVIII to the white pulp where conventional dendritic cells (DCs) prime helper T cells, which then differentiate into follicular helper T (Tfh) cells. Toll-like receptor 9 (TLR9) stimulation accelerated Tfh responses, Germinal Center and inhibitor formation, while systemic administration of FVIII alone in hemophilia A mice increased frequencies of monocyte-derived and plasmacytoid DCs. Moreover, FVIII enhanced T cell proliferation to another protein antigen (ovalbumin), and inflammatory signaling-deficient mice were less likely to develop inhibitors, indicating that FVIII may have intrinsic immunostimulatory properties. Ovalbumin, which, unlike FVIII, is absorbed into the RPMF compartment, fails to elicit T cell proliferative and antibody responses when administered at the same dose as FVIII. Altogether, we propose that an antigen trafficking pattern that results in efficient in vivo delivery to DCs and inflammatory signaling, shape the immunogenicity of FVIII.

Type I interferons (IFN) are central players in the pathogenesis of systemic lupus erythematosus (SLE) and the up-regulation of interferon-stimulated genes (ISGs) in SLE patients is subjected to increasing scrutiny as for its use in diagnosis, stratification and monitoring of SLE patients. Determinants of this immunological phenomenon are yet to be fully charted. The purpose of this systematic review was to characterize expressions of ISGs in blood of SLE patients and to analyze if they associated with core demographic and clinical features of SLE. Twenty cross-sectional, case-control studies comprising 1033 SLE patients and 602 study controls could be included. ISG fold-change expression values (SLE vs controls), demographic and clinical data were extracted from the published material and analyzed by hierarchical cluster analysis and generalized linear modelling. ISG expression varied substantially within each study with IFI27, IFI44, IFI44L, IFIT4 and RSAD2, being the top-five upregulated ISGs. Analysis of inter-study variation showed that IFI27, IFI44, IFI44L, IFIT1, PRKR and RSAD2 expression clustered with the fraction of SLE cases having African ancestry or lupus nephritis. Generalized linear models adjusted for prevalence of lupus nephritis and usage of hydroxychloroquine confirmed the observed association between African ancestry and IFI27, IFI44L, IFIT1, PRKR and RSAD2, whereas disease activity was associated with expression of IFI27 and RNASE2. In conclusion, this systematic review revealed that expression of ISGs often used for deriving an IFN signature in SLE patients were influenced by African ancestry rather than disease activity. This underscores the necessity of taking ancestry into account when employing the IFN signature for clinical research in SLE.

Mechanisms thought to regulate activated factor VIII (FVIIIa) cofactor function include A2-domain dissociation and activated protein C (APC) cleavage. Unlike A2-domain dissociation, there is no known phenotype associated with altered APC cleavage of FVIII, and biochemical studies have suggested APC plays a marginal role in FVIIIa regulation. However, the in vivo contribution of FVIIIa inactivation by APC is unexplored. Here we compared wild-type B-domainless FVIII (FVIII-WT) recombinant protein with an APC-resistant FVIII variant (FVIII-R336Q/R562Q; FVIII-QQ). FVIII-QQ demonstrated expected APC resistance without other changes in procoagulant function or A2-domain dissociation. In plasma-based studies, FVIII-WT/FVIIIa-WT demonstrated dose-dependent sensitivity to APC with or without protein S, whereas FVIII-QQ/FVIIIa-QQ did not. Importantly, FVIII-QQ demonstrated approximately fivefold increased procoagulant function relative to FVIII-WT in the tail clip and ferric chloride injury models in hemophilia A (HA) mice. To minimize the contribution of FV inactivation by APC in vivo, a tail clip assay was performed in homozygous HA/FV Leiden (FVL) mice infused with FVIII-QQ or FVIII-WT in the presence or absence of monoclonal antibody 1609, an antibody that blocks murine PC/APC hemostatic function. FVIII-QQ again demonstrated enhanced hemostatic function in HA/FVL mice; however, FVIII-QQ and FVIII-WT performed analogously in the presence of the PC/APC inhibitory antibody, indicating the increased hemostatic effect of FVIII-QQ was APC specific. Our data demonstrate APC contributes to the in vivo regulation of FVIIIa, which has the potential to be exploited to develop novel HA therapeutics.

OBJECTIVES Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation. METHODS We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were categorized as no improvement; improvement (resolution of at least 1 symptom while remaining on therapy); and complete resolution of symptoms. RESULTS A total of 239 subjects (12.1 ± 4.1 years [mean ± standard deviation], 70% girls) were included. The identified characteristics of childhood GP were broad with idiopathic GP being the most common etiology. Outcomes over a median of 22 months (25%-75%: 9.0-45.5 months) were 34.8% no improvement, 34.8% some improvement, and 30.3% with complete symptom resolution. Compared to younger children, adolescents had a higher female predominance (P

Human breast cancer which affects 1/8 women is rare at a cellular level. Even in the setting of germline BRCA1/BRCA2, which is present in all breast cells, solitary cancers or cancers arising at only several foci occur. The overwhelming majority of breast cells (109–1012 cells) resist transformation. Our hypothesis to explain this rareness of transformation is that mammary oncogenesis is regulated by the cell of origin’s critical window of differentiation so that target cells outside of this window cannot transform. Our novel hypothesis differs from both the multi-hit theory of carcinogenesis and the stem/progenitor cell compartmental theory of tumorigenesis and utilizes two well established murine transgenic models of breast oncogenesis, the FVB/N-Tg (MMTV-PyVT)634Mul/J and the FVB-Tg (MMTV-ErbB2) NK1Mul/J. Tail vein fibroblasts from each of these transgenics were used to generate iPSCs. When select clones were injected into cleared mammary fat pads, but not into non-orthotopic sites of background mice, they exhibited mammary ontogenesis and oncogenesis with the expression of their respective transgenes. iPSC clones, when differentiated along different non-mammary lineages in vitro, were also not able to exhibit either mammary ontogenesis or oncogenesis in vivo. Therefore, in vitro and in vivo regulation of differentiation is an important determinant of breast cancer oncogenesis.

Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers.

The present study reports five metazoan parasites recorded from silver kob (Argyrosomus inodorus). Five fish were collected monthly (n=55) for 11 months in 2017–2018 (excluding July 2017) using conventional angling gear in Toscanini, Mile 108 and Henties Bay, northern Namibia. Fish were examined individually for ecto- and endo-parasites. Photomicrographs, drawings and measurements of parasites were made using a camera lucida and calibrated eyepiece of an Olympus (BX50) compound microscope and/or a Zeiss (Discovery V8) camera calibrated on a Leica dissecting microscope. Amongst species found, monogeneans including Diplectanum sciaenae van Beneden & Hesse, 1863, two species of Calceostoma van Beneden, 1858, one species of Sciaenacotyle Mamaev, 1989 and one acanthocephalan Corynosoma australe Johnston, 1937 were found and are reported here. This is the first study of parasites found from silver kob of the Atlantic Ocean. Silver kob has potential to be used as a mariculture species. In addition to mariculture, information obtained from this study may also be used as a baseline for stock structure and biological tagging.Significance: Silver kob has potential to be used as a mariculture species. Information obtained from this study will therefore form awareness to future mariculture silver kob farmers in terms of parasites that can infest and infect silver kob, hence making it possible to apply specific prevention and control measures. In addition to mariculture, results obtained from this study may be used as a baseline for biological tagging for stock structure assessment using parasites.

This study evaluated the effects of dietary Aloe vera polysaccharides on growth performance, feed utilization, hemato-biochemical parameters, and resistance against low water pH in African catfish (Clarias gariepinus) fingerlings. Fish were divided into five triplicate groups before being fed feeds supplemented with 0% (control), 0.5%, 1.0%, 2.0%, and 4.0% A. vera/kg diet for 8 weeks. Fish fed 1.0% A. vera/kg diet had significantly increased (P

Background Powerful constitutive and inducible transgenic / bitransgenic / tritransgenic murine models of breast cancer have been used over the past two decades to shed light on the molecular mechanisms by which the given transgenic oncogenes have interacted with other cellular genes and set in motion breast cancer initiation and progression. However, these transgenic models, as in vivo models only, are expensive and restrictive in the opportunities they provide to manipulate the experimental variables that would enable a better understanding of the molecular events related to initial transformation and the target cell being transformed. Methods To overcome some of these limitations, we derived oncogene-containing induced pluripotent stem cell (iPSC) clones from tail vein fibroblasts of these transgenic mice and manipulated them both in vitro and in vivo in non-transgenic background mice. We created the iPSC clones with a relatively low M.O.I, producing retroviral integrations which averaged only 1 to 2 sites per retroviral plasmid construct used. Results Most iPSC clones derived from each group displayed an essentially normal murine karyotype, strong expression of the exogenous reprogrammable genes and significant expression of characteristic endogenous murine surface stem cell markers including SSEA-1 (CD15), PECAM-1 (CD31), Ep-Cam (CD326), and Nectin (CD112), but no expression of their transgene. A majority (75%) of iPSC clones displayed a normal murine karyotype but 25% exhibited a genomically unstable karyotype. However, even these later clones exhibited stable and characteristic iPSC properties. When injected orthotopically, select iPSC clones, either constitutive or inducible, no longer expressed their exogenous pluripotency reprogramming factors but expressed their oncogenic transgene (PyVT or ErbB2) and participated in both breast ontogenesis and subsequent oncogenesis. When injected non-orthotopically or when differentiated in vitro along several different non-mammary lineages of differentiation, the iPSC clones failed to do so. Although many clones developed anticipated teratomas, select iPSC clones under the appropriate constitutive or inducible conditions exhibited both breast ontogenesis and oncogenesis through the same stages as exhibited by their transgenic murine parents and, as such, represent transgenic surrogates. Conclusions The iPSC clones offer a number of advantages over transgenic mice including cost, the ability to manipulate and tag in vitro, and create an in vitro model of breast ontogeny and oncogenesis that can be used to gain additional insights into the differentiated status of the target cell which is susceptible to transformation. In addition, the use of these oncogene-containing iPSC clones can be used in chemopreventive studies of breast cancer.

Background Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that regulates food intake and energy hemostasis. BDNF also promotes neurogenesis, neuroplasticity, and neuroprotection. There are conflicting reports regarding how intermittent fasting affects circulating BDNF levels. We tested the hypothesis that 4-week intermittent fasting from dawn to sunset (4-week-IF) would decrease circulating BDNF levels in subjects with metabolic syndrome and healthy subjects. Methods We conducted pilot studies in subjects with metabolic syndrome and healthy subjects who fasted from dawn to sunset for more than 14 h for four consecutive weeks. We measured serum BDNF levels and metabolic parameters before 4-week-IF, at the end of 4th week during 4-week-IF, and one week after 4-week-IF. Results We enrolled 28 subjects, 14 with metabolic syndrome (women/men:6/8) with a mean age of 59 years and 14 healthy subjects (women/men:1/13) with a mean age of 32 years. Overall, BDNF levels decreased at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (mean paired difference = −98.5 ng/ml, P = 0.0006). When subjects with metabolic syndrome were compared with healthy subjects, subjects with metabolic syndrome had a lower mean paired reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (BDNF mean paired difference = −27.6 ng/ml vs. −169.5 ng/ml, P = 0.003). Multivariate linear regression analysis showed a positive correlation between the change in tumor necrosis factor-alpha and change in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome (P = 0.040) and healthy subjects (P = 0.007). The change in weight and body mass index independently predicted the change in BDNF levels 1 week after 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome. Conclusion Four-week-IF resulted in a reduction in the BDNF levels at the end of 4th week during 4-week-IF. Higher BDNF levels and a lower reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome than healthy subjects suggest a potential BDNF resistance similar to insulin and leptin resistance in metabolic syndrome. A positive correlation between the change in BDNF and change in tumor necrosis factor-alpha levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF suggests that BDNF is a biomarker of inflammation and endothelial dysfunction in addition to its neurotrophic and anorexigenic features.

This study evaluated the effects of dietary Allium sativum and Aloe vera polysaccharides mixtures on growth performance, feed utilization, hematological parameters, resistance against low water pH, and whole body composition of African catfish (Clarias gariepinus) juveniles. Fish were divided into 5 triplicate groups before being fed diets supplemented with 0% (control), 0.5%, 1.0%, 2.0% and 4.0% A. vera and A. sativum polysaccharides mixture /kg diet (1:1 proportion). Fish fed 1.0% and 0.5% A. vera-A. sativum mixture supplemented diet had a significant increase (P < 0.05) in growth compared to unsupplemented ones, and those fed 2.0% and 4.0%. Similarly, among dietary groups, feed utilization indices were significantly improved (P < 0.05) in fish fed 1.0% A. vera-A. sativum mixture supplemented diet when compared to unsupplemented ones, and those fed 2.0% and 4.0%. The optimum dietary A. vera-A. sativum mixture inclusion level was estimated to range between 0.66% and 0.8%. Overall, A. vera-A. sativum mixture extracts had improved hematological indices when compared to unsupplemented fish. Fish fed 1.0% A. vera-A. sativum mixture had the highest survival probability throughout the low water pH (5.0 – 57) challenge period. Moreover, fish fed diets supplemented with 1.0%, 2.0%, and 4.0% A. vera-A. sativum mixture had significantly lower lipid content (P < 0.05) among the various groups. To fully optimize these extracts as dietary supplement in aquaculture, further similar and extended studies are deemed important.

The COVID-19 pandemic has mandated the use of virtual interactions in medical school. Although this falls mainly in the area of didactic instruction, of necessity, it has extended to the critical Admissions Process and the Medical School Interview itself. The California University of Science and Medicine (CUSM) with their flipped classroom approach had previously entered a virtual space of instruction even before COVID-19. Because CUSM was, in a sense, already committed to ‘virtual’ education, in the face of the COVID-19 pandemic, CUSM focused not on what it might lose but what it might gain and what their applicants to medical school might gain with the virtual format. The COVID-19 pandemic provided a unique opportunity to initially compare the Virtual Interview with the traditional On-Campus (In-Person) Interview during the hybrid 2020 year when the COVID-19 pandemic began. The Virtual Interview was patterned after the On-Campus Interview with some modifications. The same faculty conducted both interviews. A number of inherent advantages of the Virtual Interview surfaced to these faculty interviewers based on their subjective observations and conclusions. The overall interviewee satisfaction with the Virtual Interview was very positive based on their subjective observations and conclusions. The objective data from the Virtual Interviews compared to the On-Campus Interviews in the hybrid year resulted in a greater percentage of both offers of acceptance (p = .001) and matriculations (p = .001). In order to strengthen our initial observations, we expanded our study to include 2 pre-COVID-19 years (2018, 2019) of exclusively On-Campus interviews (n = 743) and 1 additional COVID-19 year (2021) of exclusively Virtual Interviews (n = 529). In this expanded study, interviewee demographics were not confounding and the Virtual Interview gave rise to overall greater interviewee satisfaction (p = .001), a trend to greater interviewer satisfaction and a greater percentage of both offers of acceptance (p = .047) and matriculations (p = .036).

Five Cape fur seals, Arctocephalus pusillus pusillus, 1 dusky kob, Argyrosomus coronus, and 55 silver kob, A. inodorus, collected from Cape Cross, Henties Bay, and Skeleton Coast Park, Namibia, were examined for acanthocephalans. Adults of Bolbosoma vasculosum and Corynosoma australe were recovered from 5 Cape fur seals, and cystacanths of C. australe from the single dusky kob and 3 of the silver kobs that were examined. This is the first record of B. vasculosum and the second of C. australe from the Namibian coast. Scanning electron microscopy of specimens of C. australe revealed features such as bursal papillae and micropores both on the proboscis hook surfaces and across the epidermal surface of the trunk. X-ray analyses of gallium cut hook, egg, and spines of C. australe are presented with analyses of spines of Corynosoma strumosum for comparison.

Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration. Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 mu g/ml in pigeons, 12.97 mu g/ml in chickens, 14.24 mu g/ml in cockatiels, and 47.81 mu g/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 mu g/ml in pigeons, 21.59 mu g/ml in chickens, 32.03 mu g/ml in cockatiels, and 55.96 mu g/ml in falcons. Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability.

In this study we develop a 32-year (1982–2013) otolith biochronology of the commercially important deepwater hake Merluccius paradoxus in the northern Benguela, Namibia. Mean annual growth (mm) calculated from 140 thin-sectioned M. paradoxus otoliths were compared with change in mean length at age 3 to age 4 determined from Namibian whole-otolith-read age-length keys (ALKs). Annual growth rates calculated from the two methods (overlapping 2000–2013) were strongly positively correlated (ρ = 0.730, n = 14, p < 0.01). This indirectly validated annual age determination of M. paradoxus, the accuracy of otolith chronologies, and the ability of ALKs to capture annual variability in fish growth. Annual M. paradoxus growth rates were significantly positively correlated with the July–September upwelling index 1982–2013 at 30°S, (ρ = 0.414, n = 32, p < 0.05) and positively correlated with August mean chlorophyll-a concentrations (as indicator for primary production) 2002–2013 in the 28–30°S area (ρ = 0.734, n = 12, p < 0.01). Annual M. paradoxus growth rates significantly negatively correlated with October (austral spring) sea surface temperatures in the 24–28°S area (ρ = −0.381, n = 32, p < 0.05). This Orange-River Namaqua upwelling cell corresponds to the area where juvenile and young adult M. paradoxus live, suggesting growth rate strongly responds to local forcing. We also determined that mean length-at-age 3 calculated from ALKs (current and literature) significantly increased from 1977 through 2016 at 0.075 cm.year–1 (t = 3.04, df = 41, p = 0.004), while length-at-age 8 significantly decreased at 0.25 cm.year–1 (t = −3.59, df = 30, p = 0.001). Both trends may indicate fisheries-induced adaptive changes. M. paradoxus occurring at >300 m bottom depth, are thus strongly influenced by fisheries. As an upper-level demersal predator, this species integrates signals throughout the food web to provide a unique “view from the top” of long-term changes in the northern Benguela upwelling system. These results provide background ranges of growth variability and context for what will likely be negative impacts of predicted decreases in future upwelling.

Given the success of B cell depletion therapy in multiple sclerosis (MS), deeper understanding of pathogenic B cells will be key in developing novel treatments. Notably, B cell depletion therapy leaves plasma cells and immunoglobulin levels largely intact, indicating that B cells provide pathogenic functions beyond antibodies. To better understand this, we recently developed a novel B cell-dependent, antibody-independent experimental autoimmune encephalomyelitis (EAE) mouse model of MS featuring immunoreactivity to the extracellular domains of myelin proteolipid protein (PLPECD). In contrast to a B cell-independent EAE model, we demonstrate here that PLPECD induced EAE in WT but not B cell-depleted mice, and that established disease was ameliorated by B cell depletion. We tested antigen presentation by B cells through mixed bone marrow chimeras and demonstrate that mice in which MHC II deficiency is restricted to B cells alone failed to exhibit EAE compared to MHC II sufficient mice. Given that HLA class II is the largest molecular link to MS incidence and CD4 T cells are causative in EAE, we tested B cells’ influence on CD4 T cells. In the absence of B cells, we observed not only lower activation and proliferation of CD4 T cells, but also noted a lower proinflammatory functional profile amongst the activated cells. Further, adoptively transferred CD4 T cells derived from B cell-depleted donors induced significantly less EAE compared to those from B cell-sufficient donors. These results demonstrate that antigen presentation by B cells plays a critical role in the activation, proliferation, function and pathogenicity of autoreactive CD4 T cells in demyelinating disease. Supported by grants from NIAID/NIH AI156123 and US Veterans Affairs I01BX003677.

Understanding and validating annual structures in fish otoliths are important for stock assessments and fisheries ecology. Biannual translucent zone formation has been demonstrated for 3–21 months old Namibian shallow-water hake Merluccius capensis. This paper addresses the hypothesis that the pattern continues in older fish. Otolith zone periodicity was studied for four cohorts hatched in July of 1996, 1998, 2002 and 2005, based on modal progression analysis (n = 1059). Edge analysis and marginal increment analysis were performed on otoliths representing eleven months of the year from port samples (n = 1153) from the years 2007–2015. Two to three translucent (T)-zones are formed on the hake otoliths each year, one or two between austral summer and autumn (January to April) and one in winter–spring (between July and October). Annual zones are usually the T2, T5, T8 zones (likely every third T-zone). Annual zones are not distinguishable from pseudo-annuli under the light microscope, and therefore otolith length measurements (OL) at each T-zone should be used as a guide for assigning age (9, 15 and 19 mm OL for ages 1, 2 and 3 respectively). Otolith T-zones are associated with both warm and cold periods, when they are presumably limited by temperature or dissolved oxygen concentration as well as food availability and feeding efficiency at both ends of their tolerance range. The most noticeable factor influencing the formation of translucent zones in otoliths is fish condition, not always linked with spawning (not always linked with high GSI). M. capensis otolith zonation is thus linked with their endogenous adaptation to the ecosystem, their fish physiology and also regulated by environmental variability.

The hypothesis that fast growth rates demonstrated for 3–21-month-old Merluccius capensis continue for older fish is tested. Cohort-specific growth rates of M. capensis between 6 and 65 cm total length were described using a von Bertalanffy growth function (VBGF) fitted to annual/bi-annual research survey length-frequency distributions (LFDs) from 1995 to 2011 and monthly commercial LFDs from 1998 to 2011. These data were combined with cohort analysis of younger fish from seal scat data to provide cohort-specific growth rates for cohorts hatched from 1994 to 2008. The fitted VBGF gave L t (cm) = 108.6*{1-exp[–0.199*( t (y) + 0.025)]}. M. capensis grow between 1.4 and 0.8 cm month −1 from ages 1 to 5 years, varying by 0.2 cm month −1 among cohorts. This is about twice as fast as growth rates previously estimated from otolith methods, which therefore need to be re-evaluated. It follows that M. capensis should have higher natural mortality rates and a greater stock productivity than previously believed, emphasizing the need to review this in the current stock assessment approaches.

This work investigated the potential effects of dietary garlic (Allium sativum) crude polysaccharide (GPE) (0, 0.5, 1.0, 2.0, and 4.0%/kg diet) on growth, haematological parameters, whole body composition, and resistance against low pH in African catfish, Clarias gariepinus juveniles. At the end of 60 days, fish fed GPE supplemented diets had significantly increased (P 0.05) was observed in the cumulative survival among dietary groups following a challenge with low pH, except somewhat high survival in garlic-supplemented fish especially at 72 h. Similarly, no significant difference (P > 0.05) was presented in the whole body composition and organo-somatic indices among groups. Based on the second order polynomial analysis, dietary inclusion level less than or equal to 1.88% of garlic/kg diet is estimated suitable to support growth, feed utilization, and ultimately health in C. gariepinus juvenile culture. Keywords: African catfish, Aquaculture, Clarias gariepinus, Garlic, herbs, Immunostimulants

Transmission angle control is well studied for both crank rocker and Grashof crank slider mechanisms. However, non-Grashof slider-crank mechanisms have received less attention. For these mechanisms, the fully rotatable crank constraint is removed increasing the complexity of the problem. Furthermore, methods of linkage synthesis by optimization are becoming more prevalent. When optimizing a mechanism, it is important to prevent the evaluation of non-constructible and undesirable linkages. Presented here is a method of solution rectification by means of transmission angle control for slider-crank mechanisms which can be used to parameterize a problem to prevent the evaluation of invalid linkages. The solution is kept general to include fully rotatable crank slider mechanisms as well. The solution considers both crank driven and slider driven mechanisms as well as a reversible driver mechanism. An example is provided to demonstrate the method. It will be shown that by defining a transmission angle, valid linkages can be generated preventing the evaluation of invalid solutions.

Variations in atmospheric conditions can be important factors influencing temperature dynamics within the active layer of a soil. Solar radiation and air temperature can directly alter ground surface temperatures, while variations in wind and precipitation can control how quickly heat is carried through soil pores. The presence of seasonal snow cover can also create a thermal barrier between the atmosphere and ground surface. This study examines the relation between atmospheric conditions and ground temperature variations on a deglaciated island along the Western Antarctic Peninsula. Ground temperatures were most significantly influenced by incoming solar radiation, followed by air temperature variations. When winter months were included in the comparison, the influence of air temperature increased while solar radiation became less influential, indicating that snow cover reflected solar radiation inputs, but was not thick enough to insulate the ground. When ground temperatures were compared to atmospheric conditions of preceding weeks, seasonal temperature peaks 1.6 m below ground were best related to seasonal air temperature peaks from the previous two weeks. The same ground temperature peaks were best related to seasonal solar radiation peaks of seven weeks prior. This difference was a result of temperature lags within the atmosphere.

For more than sixty years the Antarctic Peninsula has experienced significant temperature increases that have accelerated glacial retreat. Glacial losses, along with the relatively warm and moist climatic conditions of the region, have increased the rate of soil development. The objective of this study is to study the properties and genesis of soils at Cierva Point, which is located in the zone of maximum warming along the western Antarctic Peninsula. Cierva Point is a terraced, steeply sloping, ice-free peninsula containing a small retreating glacier. The peninsula contains a large penguin rookery and significant areas of moss buildup. Twenty-seven soils were described; physical and chemical properties from each horizon were analyzed. Four categories of soil were identified: acidic (pH 5), moss-dominated (high organic matter accumulations), and ornithogenic (high phosphorus accumulations). Neutral soils were newly formed soils which had undergone the least development and were located closest to the glacier margin. Acidic soils were located farthest from the glacier margin, allowing for a greater nutrient leaching to occur; these soils have extremely low pH values (as low as 3.5) but did not have the high phosphorus accumulations found in ornithogenic soils or the high soil carbon content found in moss-dominated soils. In a region with rapidly retreating glaciers, such as the Antarctic Peninsula, proximity to the glacier margin becomes an important factor determining soil properties. Soils farther from the glacier have had more time to be affected by leaching, penguin activity, and moss buildup.

Shallow-water hake (Merluccius capensis) is of considerable ecological and economic importance in the Benguela Current Large Marine Ecosystem in South Africa and Namibia. Optimal management of the resource is currently constrained by the limited understanding of migration patterns and population (stock) structure. We combined data from multiple demersal trawl surveys from the entire distribution area to estimate growth rate, mortality and spatial and temporal patterns of M. capensis. Analyses were conducted using the geostatistical model GeoPop. The complexity of the model and the amount of data required a new level of soft- and hardware performance. This was achieved by utilizing Template Model Builder and high-end computational hardware (Amazon Elastic Compute Cloud, EC2). The data and the model enabled us to follow the distribution and infer movements of M. capensis from the recruitment/nursery areas, through the juvenile phase and the adults’ migration to the spawning areas outside/upstream of the nursery areas. This revealed some previously unknown migration patterns and indicated natal homing and the existence of three primary population components in the region, namely the Walvis (central and northern Namibia), the Orange (Southern Namibia—Northern SA) and the Agulhas (Southern part of SA) components. Our results also indicated substantial regional differences in mortality. We recommend that fisheries assessment, advice and management take consideration of these aspects of the distribution and population (stock) structure of M. capensis in the Benguela Current Large Marine Ecosystem.

The soils of the South Shetland Islands, Antarctica are considered weakly developed. Chemical weathering processes are generally considered to be negligible except in areas that receive large additions of seabird guano. In this paper we describe and analyze 19 soils on Hurd Peninsula, Livingston Island in the South Shetland Island Archipelago. The soils were classified according to US Soil Taxonomy and were generally weakly developed Gelorthents, Humigelepts and Haplorthels. However, B horizon formation, rubification and increases in extractable Fe and Al were observed on toposequences of raised beaches. The deposition of tephra and/or guano is likely responsible for the chemically driven processes. Guano deposits contain phosphates and oxalic acid, causing phosphatization and/or dissolution of silicates. Input of tephra with easily weatherable minerals may account for metastable mineral formation. Tephra deposition in the oldest raised beaches has formed a fine-textured mantle overlying the coarser textured subsoils. Highly weatherable tephra, as opposed to guano deposition, appears to influence soil formation at Hurd Peninsula.

We use gonad- and body-weight data from 54,000 samples of Merluccius capensis and Merluccius paradoxus collected in all months of the years between 1991 and 2013 to infer peak spawning periods and areas in the Benguela Current Large Marine Ecosystem. We develop and apply a new gonadosomatic index threshold for identification of spawning individuals. Spawning M. capensis were observed throughout the study area, mainly in areas of about 100 m bottom depth. The highest proportions of spawning M. capensis females in the northern Benguela region were observed off central Namibia between 24.0 and 26.0°S. In the southern Benguela, peaks in the proportions of spawning M. capensis were observed in two areas off the South African West Coast (31.0–32.5°S and 34.5–36.0°S), whereas spawning females off the South African South Coast (east of 20°E) appeared to be more evenly distributed in space. Seasonality differed between areas. In the northern Benguela, the main spawning season of M. capensis appeared to be the austral winter (July–September, peaking in August), while off the South African South Coast, the main spawning season is suggested to be in summer (around January). Between these two extremes, on the western Agulhas bank in the southern Benguela, spawning peaks were observed in both summer and winter. These peaks largely coincided with peaks in phytoplankton production that are linked to upwelling conditions in the region. Hake condition decreased subsequent to the development of the gonads. The annual spawning cycle differed between small and large M. capensis. The current October–closure of the fishery in Namibia may not match the peak spawning in August/September and may need to be shifted to earlier in the year. Spawning M. paradoxus were mainly found in areas of 200–650 m bottom depths. In the northern Benguela, spawning M. paradoxus were observed as far north as 25°S in August. The proportion of spawning females peaked between 34.5°S and 36.5°S off the West Coast, and between 23.0°E and 26.5 °E off the South Coast. It was suggested that M. paradoxus spawn throughout the year off the South African coast, with increased intensity around March and August–October. The finding of multiple spawning seasons and areas of both M. capensis and M. paradoxus strongly suggest multiple stocks (reproductive units).

Background Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. Study Design Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO. Setting & Participants Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure. Intervention DPO versus EPO. Outcomes All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Measurements Unadjusted and adjusted HRs from Cox proportional hazards regression models. Results Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25). Limitations Nonrandom treatment assignment, potential residual confounding. Conclusions In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

Otoliths collected at least monthly from scat samples of Cape fur seals Arctocephalus pusillus are used to show that shallow-water hake Merluccius capensis from the northern Benguela develop three translucent zones in their first 1·5 years of life. The novel sampling approach provided otoliths that belonged to four M. capensis cohorts of approximate known age (hatched in 1996, 1998, 2002 and 2005), allowing age verification. Following spawning in austral winter, translucent zones consistently formed first in summer and autumn (T1), then in winter and spring (T2) and again in summer and autumn (T3), with no difference in appearance of the zones (biannuli) for the four cohorts considered. The second translucent zone is usually the first true annulus (year mark). It forms during July to September in fish of 15-20 cm total length (LT ). Formation of the translucent zones appears to be determined by fish length or age, rather than by exogenous cues. It is suggested that length measurements should be used to help determine the first age group; fish with a translucent zone marked at otolith lengths >7·5 mm should be termed 1 year-old fish. Ages of M. capensis used in previous stock assessment models have been overestimated. Biannuli are an unusual occurrence in fish otoliths in general, but have been observed in other Merluccius species.

The effects of climate change along the climatically sensitive Western Antarctic Peninsula (WAP) on active layer dynamics have just begun to be monitored. But extreme climates and difficult access make borehole installation here challenging. This study was designed to examine the ability of two commonly used, minimally intrusive techniques (the Stefan and Kudryavtsev equations) to predict active layer temperature dynamics and maximum active layer thickness (ALT) on Amsler Island, on the WAP. The ALT in soils and unconsolidated materials was predicted to be between 4.7 and 8.7 m, and between 11.9 and 18.6 m in bedrock, consistent with measurements made in a 14.6 m deep borehole. The thermal model HYDRUS accurately predicted temperature dynamics at several monitored borehole depths. The success of the HYDRUS method indicates that the model can be a useful tool in predicting active layer temperatures and approximating ALTs in regions that are too difficult to install monitoring boreholes. Copyright © 2015 John Wiley & Sons, Ltd.

We investigate the spatial distributions of juvenile and adult hake Merluccius capensis on the Namibian continental shelf using data from 25 biomass surveys (1990–2007) to identify (i) nursery/spawning areas, their spatial or temporal separation and change and (ii) length, depth and latitude preference patterns. The density of fish (number-of-fish per 30-min-haul) was examined in relation to fish total length (TL) and latitude and TL and bottom depth. Nursery aggregations were most frequent in central (22–25°S) and southern (26–29°S) Namibia, increasing in density in the south since 2000. Hatch dates of ≤17 cm fish were calculated from juvenile growth rates. Peaks occurred in winter and summer-autumn in the centre and slightly later in the south. Spawning areas appear to have shifted southward since the late 1970s, showing the plasticity of this stock as a response to fishing pressure and environmental variability and change. Merluccius capensis show a stable pattern of latitude preference over the 25 surveys examined. They first occur on the mid-shelf

Activated factor VIII (FVIIIa) is an essential cofactor in the intrinsic tenase (Xase) enzyme complex that generates factor Xa and propagates clot formation. The FVIIIa heterotrimer is comprised of a metal ion linked dimer (A1/A3-C1-C2 domains) that is associated with the A2 domain by weak non-covalent interactions. Regulation of FXa formation by the intrinsic Xase enzyme complex occurs by FIXa inhibition and mechanisms contributing to FVIIIa inactivation, including: 1) rapid A2 domain dissociation and 2) activated protein C (APC) cleavage of FVIIIa. While FVIIIa inactivation by APC is considered important, there are surprisingly no in vivo studies documenting the hemostatic role of APC in FVIIIa regulation. Further, published data demonstrate APC cleavage of FVIIIa at physiologic protein concentrations occurs over hours while A2 dissociation occurs rapidly over minutes. Thus, it is thought that the predominant mechanism of FVIIIa inactivation is A2 dissociation and APC likely plays a marginal role in FVIIIa regulation. Additionally, unlike described A2 mutations that enhance dissociation and cause hemophilia A (HA), there is no known disease state attributed to altered FVIIIa cleavage by APC. This is in contrast to FVIII's homologous protein, FVa, whereby resistance to APC cleavage is the most common inherited thrombophilia (FV-Leiden [FVL]). Understanding the physiologically relevant mechanisms of FVIIIa inactivation has immediate clinical applicability for understanding safety considerations in HA therapeutics that bypass FVIIIa regulation (FVIII mimetic antibodies, e.g. emicizumab). Further, as evidenced by successful hemophilia B gene therapy trials using a gain of function FIX variant (FIX-Padua), altering FVIIIa inactivation could be exploited for therapeutic benefit in the setting of gene transfer. We aimed to determine the in vivo hemostatic role of APC in FVIIIa regulation and pair these studies with purified system analysis. We introduced Arg to Gln mutations at FVIII APC cleavage sites (R336Q and R562Q, herein called FVIII-QQ) on a B-domain deleted FVIII (FVIII-WT) backbone and produced recombinant FVIII-QQ and FVIII-WT. Unlike FVIII-WT, western blot analysis of FVIII-QQ incubated with APC and phospholipids had no evidence of cleavage. Enzyme kinetic studies using purified components demonstrated no appreciable difference in the Km or Vmax for FX within the intrinsic Xase enzyme complex or A2 dissociation of FVIII-QQ relative to FVIII-WT. These data confirmed no unexpected differences in FVIII-QQ relative to FVIII-WT. To begin to evaluate the role of APC in FVIIIa regulation, we measured thrombin generation in murine and human HA plasma reconstituted with FVIII-QQ or FVIII-WT in the presence of increasing APC concentrations. The IC50 of APC was 2-3-fold higher for FVIII-QQ than FVIII-WT. To evaluate the in vivo hemostatic effect of APC in FVIIIa regulation, HA mice were infused with FVIII-QQ or FVIII-WT and evaluated by tail clip injury and 7.5% FeCl3 carotid artery occlusion models. Required doses of FVIII-QQ to normalize blood loss from a tail clip assay and time to vessel occlusion in a FeCl3 assay were 4-5 fold lower than necessary FVIII-WT doses; the superior hemostatic effect of FVIII-QQ supported the physiologic significance of APC in FVIIIa inactivation. To isolate the role of APC in FVIIIa regulation from APC inactivation of FVa, we backcrossed HA mice with FVL mice to create homozygous HA/FVL mice. HA/FVL mice were infused with FVIII-QQ or FVIII-WT and underwent tail clip assay analysis. Doses of FVIII-QQ required to normalize blood loss were again less than FVIII-WT. To further isolate the enhanced hemostatic effect of FVIII-QQ to APC resistance, we performed the tail clip assay in HA/FVL mice infused with FVIII-QQ or FVIII-WT in the presence or absence of MPC1609, an antibody that blocks murine APC function (Xu et al. J Thromb Haemost 2008). In the presence of MPC1609, the same dose of FVIII-WT and FVIII-QQ was required to normalize blood loss (Figure 1). Collectively, our in vitro and in vivo data support the physiologic significance of APC in FVIIIa regulation. To our knowledge these data are the first to demonstrate the in vivo hemostatic effect of APC in FVIIIa inactivation. Our data may be translated to rationally exploit APC regulation of FVIIIa to develop novel HA therapeutics or further delineate safety considerations in therapies that bypass FVIIIa regulation. Figure 1 Disclosures Camire: Pfizer: Research Funding. George:University of Pennyslvania: Employment; Pfizer: Consultancy; Avrobio: Membership on an entity's Board of Directors or advisory committees.

Wilhelm, M. R., Roux, J-P., Moloney, C. L., and Jarre, A. 2013. Data from fur seal scats reveal when Namibian Merluccius capensis are hatched and how fast they grow. – ICES Journal of Marine Science, 70: . Scat samples were collected regularly at several breeding colonies of Cape fur seals along the Namibian coast. Merluccius capensis otoliths were obtained from these samples, identified, and measured. Cohorts were easily distinguishable using otolith length measurements converted to fish total length. Growth rates of 2- to 21-month-old hake and hatch dates for each of 15 cohorts were estimated from September 1994 to October 2009 (1994–2008 cohorts) using a Schnute growth function and a non-linear mixed-effects model. The function describing growth of these young hake was length Lt (cm) at age t (years) Lt = 3.17 + (25.0 − 3.17) × [1 − e−0.665 × (t − 0.140)]/[1 − e−0.665 × (1.74–0.140)]. Cohort-specific random effects showed a population hatch date estimate of 31 July (austral winter), varying by 94 days among cohorts, from 31 May (1996 cohort) to 1 September (2004 cohort). The mean growth rate from ages 6 to 12 months was 1.26 cm month−1 for the population, ranging between 0.97 cm month−1 (1996 cohort) and 1.38 cm month−1 (2004 cohort). As this rate is almost double the previously estimated value, which is currently used in the stock assessment models, this result may have major implications for the current stock assessment results and the management of the stock. Re-examination of growth rates needs to be extended to older fish.

In Wisconsin there is concern that timber harvesting on nutrient-poor, sandy soils could lead to depletion of nutrients. This concern could become exacerbated by the increasing demand for biofuels, followed by intensified utilization practices. This project measured dry matter and macronutrient (N, P, K, Ca, and Mg) pools and major inputs (bulk precipitation, weathering + mineralization index) and outputs (leaching losses) on four treatment plots at each of five sites on sandy soils at the Governor Knowles State Forest in northwest Wisconsin: an unharvested treatment, a conventional removal of stem and branches down to a diameter of 5 cm, a removal of stem and branches down to a diameter of 10 cm, a removal of all aboveground biomass. All treatments were applied during the early winter, leaf-off period. Data collected over 2 years (2010 and 2011) were applied to a nutrient-balance equation to determine if there were treatment-related differences in nutrient accumulation or depletion. The labile soil was the leading pre- and post-harvest pool for P, K, Ca and Mg in the ecosystem. Biomass removed during Whole-tree harvests constituted ∼50% of the ecosystem nitrogen and contributed significantly to the removal of the other macronutrients. From nutrient input–output balances, N (NH 4 and NO 3 ), K, Ca, and Mg were calculated to be accumulating on all harvest treatments. During the first year after harvest (2010), N mineralization, along with P and Ca accumulation rate, was significantly greater than unharvested treatments. Nitrogen accumulation rates, along with leaching losses of N and P, were significantly lower on all harvest treatments than on unharvested treatments. There were no significant differences in mineralization rates and leaching losses among treatments for the other macronutrients. During the second year (2011), differences in N mineralization, leaching and accumulation rates had largely disappeared. Phosphorus was the only nutrient that showed a net depletion, and this depletion was detected for all harvested treatments. However, the depletion rates were so low that it would take several rotations for any P deficiencies to become apparent. The results of this study may not apply to other sandy soils.

Additional file 1. Description of interviews with key informants.

Wireworms of Agriotes lineatus, A. obscurus, A. sputator and A. sordidus were exposed to insecticide treated soil using two different control methods. One method consisted of a spray application of insecticides at doses of 50, 100, 200, and 300 g a.i. per ha. The other method consisted of a bait treatment at doses of 0.01, 0.1, 1, and 10 g a.i. per ha. Four insecticides were tested: fipronil and the neonicotinoids thiamethoxam, imidacloprid and clothianidin. In the soil treatment trial, chlorpyrifos was added as a reference treatment. The two test methods were conducted at different dates on the various species, but in equally controlled conditions. Mortality was observed after one and two (bait treatment) or three (soil treatment) weeks of exposure. Fipronil was highly lethal to each of the wireworm species tested, regardless of the method used. In general, mortality was higher compared to the neonicotinoids tested, the latter showing low or no mortality at the given dose and exposure variants. Applying fipronil in a bait formulation may decrease the amount of active ingredient per ha considerably, therefore baits may have important environmental benefits.

In a preliminary version of the NA48 experiment at the CERN SPS, in which an iron-scintillator sandwich calorimeter was used as a photon detector, the ratio of K L → πμνγ and K L → πμν decays was measured. The branching ratio BR(K L →πμνγ, E γ ∗ ≥30 MeV )/(K L → πμν ) is found to be (2.08±0.17 +0.16 −0.21 )×10 −3 , where the first error is statistical and the second systematic. The result is in agreement with theoretical predictions.

The need for a revision of the Division of Chemical Education’s “Minimum Safety Guidelines for Chemical Demonstrations” is described, along with guiding principles for the revision. The revised guidelines are included as Supporting Information.

The Cape horse mackerel stock off Namibia is assessed using a fleet-disaggregated age-structured production model including historical International Commission for the Southeast Atlantic Fisheries (ICSEAF) and current data. Data from acoustic biomass surveys, on commercial catch per unit effort and on commercial catch-at-age, were used to estimate current stock status over a range of model specifications. A management tool, the so-called management monitor graph, was introduced in order to track past management relative to stock status. Target, limit and precautionary reference points, decision rules and harvesting strategies, according to which the stock should be managed, are described and tested. The target reference point was set at maximum sustainable yield (MSY), the precautionary reference point at 80% of MSY and the limit reference point at 30% of MSY. Owing to some inconsistencies in the dataseries, evaluation of the current state of the resource is challenging, but estimates are that the resourc...

Emotionale und korperliche Misshandlungen in Kindheit und Jugend („childhood maltreatments“, CMs) werden als mogliche atiologische Faktoren des Fibromyalgiesyndroms (FMS) diskutiert. Bisher wurde nicht uberpruft, ob die Assoziation von CMs und FMS durch Mediatoren bedingt ist. CMs von konsekutiven FMS-Patienten aus 3 verschiedenen klinischen Kontexten wurden mit der deutschen Version des Childhood Trauma Questionnaire erfasst. Als mogliche Mediatoren wurden klinisches Setting, Geschlecht, Alter, komorbide depressive Storung und Inanspruchnahme medizinischer Leistungen uberpruft. Es konnten 293/328 Patienten ausgewertet werden (86% Frauen, Durchschnittsalter 50 Jahre): 16% der Patienten berichteten schweren emotionalen, 9% schweren korperlichen und 11% schweren sexuellen Missbrauch sowie 25% schwere emotionale und 13% schwere korperliche Vernachlassigung in Kindheit und Jugend. Die Haufigkeit von CMs war nicht mit Setting, Geschlecht, Alter und Inanspruchnahme medizinischer Leistungen assoziiert. Patienten mit depressiven Storungen gaben haufiger korperlichen (p=0,01) und emotionalen Missbrauch (p=0,001) sowie emotionale (p=0,0008) und korperliche Vernachlassigung (p=0,001) an als Patienten ohne depressive Storung. Komorbide depressive Storungen sind ein Mediator der Assoziation von CMs und FMS. Prospektive bevolkerungsbasierte Studien unter Kontrolle von depressiven Storungen sind notwendig, um die Bedeutung von CMs fur die Atiologie des FMS zu uberprufen.

Wilhelm-Leen ER, Hall YN, deBoer IH, Chertow GM. (Stanford University School of Medicine; University of Washington; Stanford University School of Medicine, Palo Alto, CA, USA). Vitamin D deficiency and frailty in older Americans. J Intern Med 2010; 268: 171–180. Objective. To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality. Design. Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25-hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated. Subjects. Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994. Results. 25-Hydroxyvitamin D deficiency, defined as a serum concentration

Searches for field horizontal-branch (FHB) stars in the halo of the Galaxy in the past have been carried out by several techniques, such as objective-prism surveys and visual or infrared photometric surveys. By choosing adequate color criteria, it is possible to improve the efficiency of identifying bona fide FHB stars among the other objects that exhibit similar characteristics, such as main-sequence A-stars, blue stragglers, subdwarfs, etc. In this work, we report the results of a spectroscopic survey carried out near the south Galactic pole intended to validate FHB stars originally selected from the HK objective-prism survey of Beers and colleagues, based on near-infrared color indices. A comparison between the stellar spectra obtained in this survey with theoretical stellar atmosphere models allows us to determine T eff, log g, and [Fe/H] for 13 stars in the sample. Stellar temperatures were calculated from measured (B – V) o , when this measurement was available (16 stars). The color index criteria adopted in this work are shown to correctly classify 30% of the sample as FHB, 25% as non-FHB (main-sequence stars and subdwarfes), whereas 40% could not be distinguished between FHB and main-sequence stars. We compare the efficacy of different color criteria in the literature intended to select FHB stars, and discuss the use of the Mg II 4481 line to estimate the metallicity.

Using effective temperature and metallicity derived from SDSS spectra for ~60,000 F and G type main sequence stars (0.2, Comment: 40 pages, 21 figures, emulateApJ style, accepted to ApJ, high resolution figures are available from http://www.astro.washington.edu/ivezic/sdss/mw/astroph0804.3850

Das Prostatakarzinom (PCA) ist die haufigste Krebserkrankung des Mannes in Zentral- und Westeuropa. Jahrlich erkranken etwa 202.000 Manner in Europa neu an diesem Tumor. Die kurative Behandlung des PCA per Brachytherapie gewinnt zunehmend an Bedeutung (20–30% Anteil an kurativen Behandlungen). Von auserordentlicher Bedeutung ist das initiale Staging und damit die pratherapeutische Einteilung in Risikogruppen. Die Low-dose-rate- (LDR-)Brachytherapie (SEED Implantation) unterscheidet sich bezuglich des Verfahrens, sowie der Indikation von der High-dose-rate- (HDR-)Brachytherapie (Afterloading Verfahren). Beide Verfahren finden sowohl als Monotherapie als auch kombiniert mit externer Bestrahlung Anwendung. Bei der LDR-Monotherapie wird im Bereich der Low-risk-Tumoren im 10-Jahres-Follow-up uber eine biochemische Rezidivfreiheit von bis zu 90% berichtet. Bei der kombinierten HDR-Tele- und Brachytherapie wird in Langzeitverlaufen bezuglich der Intermediate- und High-risk-Tumoren uber biochemische Rezidivfreiheiten von 80–90% berichtet. Randomisierte Studien fehlen, aber aus Anwendungsbeobachtungen und Kohortenstudien lassen sich die folgenden Anwendungsalgorithmen ableiten. Die Anwendung der LDR-Monobrachytherapie muss auf Low-risk-Tumoren beschrankt bleiben. Die kombinierte HDR-Tele- und Brachytherapie kann im Bereich der Intermediate- und High-risk-Tumoren erfolgversprechend angewendet werden. Das Outcome hangt initial entscheidend vom pratherapeutischen PSA-Wert und Gleason-Score ab. Posttherapeutisch hat der Nadir die groste Aussagekraft bezuglich der biochemischen Rezidivfreiheit.

Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.