Correspondence regarding 'Clouded leopards, the secretive top-carnivore of South-East Asian rainforests: their distribution, status and conservation needs in Sabah, Malaysia'

Correspondence regarding Wilting A, Fischer F, Bakar SA, Linsenmair KE: Clouded leopards, the secretive top-carnivore of South-East Asian rainforests: their distribution, status and conservation needs in Sabah, Malaysia. BMC Ecol 2006, 6:16

Root Traits of Perennial C\u3csub\u3e4\u3c/sub\u3e Grasses Contribute to Cultivar Variations in Soil Chemistry and Species Patterns in Particulate and Mineral-Associated Carbon Pool Formation

Recent studies have indicated that the C4 perennial bioenergy crops switchgrass (Panicum virgatum) and big bluestem (Andropogon gerardii) accumulate significant amounts of soil carbon (C) owing to their extensive root systems. Soil C accumulation is likely driven by inter- and intraspecific variability in plant traits, but the mechanisms that underpin this variability remain unresolved. In this study we evaluated how inter- and intraspecific variation in root traits of cultivars from switchgrass (Cave-in-Rock, Kanlow, Southlow) and big bluestem (Bonanza, Southlow, Suther) affected the associations of soil C accumulation across soil fractions using stable isotope techniques. Our experimental field site was established in June 2008 at Fermilab in Batavia, IL. In 2018, soil cores were collected (30 cm depth) from all cultivars. We measured root biomass, root diameter, specific root length, bulk soil C, C associated with coarse particulate organic matter (CPOM) and fine particulate organic matter plus silt- and clay-sized fractions, and characterized organic matter chemical class composition in soil using high-resolution Fourier-transform ion cyclotron resonance mass spectrometry. C4 species were established on soils that supported C3 grassland for 36 years before planting, which allowed us to use differences in the natural abundance of stable C isotopes to quantify C4 plant-derived C. We found that big bluestem had 36.9% higher C4 plant-derived C compared to switchgrass in the CPOM fraction in the 0–10 cm depth, while switchgrass had 60.7% higher C4 plant-derived C compared to big bluestem in the clay fraction in the 10–20 cm depth. Our findings suggest that the large root system in big bluestem helps increase POM-C formation quickly, while switchgrass root structure and chemistry build a mineral-bound clay C pool through time. Thus, both species and cultivar selection can help improve bioenergy management to maximize soil carbon gains and lower CO2 emissions

Vitamin D status in post-medieval Northern England: Insights from dental histology and enamel peptide analysis at Coach Lane, North Shields (AD 1711–1857)

Objectives: The post-medieval period in Europe saw a dramatic increase in metabolic bone disease related to vitamin D deficiency (VDD). Recent paleopathological work has utilized interglobular dentin (IGD) as a proxy for poor vitamin D status during development, while enamel peptide analysis allows the identification of chromosomal sex in non-adult remains. Here we explore the relationship between sex, the presence of IGD, and macroscopic markers of VDD in an industrial era assemblage from Northeast England. Materials and methods: 25 individuals (9 females, 9 males, 9 unknown sex) from the cemetery site at Coach Lane, North Shields (1711–1857) were selected for paleopathological analysis, histological assessment of IGD, and enamel peptide determination of chromosomal sex. Results: Ground tooth sections from 21 individuals were of suitable quality for detection of IGD, and enamel peptide analysis confirmed the chromosomal sex of ten individuals. Sixteen individuals (76.1%) exhibited ≥1 episode of IGD. Nine of these (42.8%) exhibited >1 episode and four (19%) exhibited ≥4 episodes in regular intervals. Male sex was significantly associated with the presence of IGD (p = 0.0351; 100% males vs. 54.5% females). Females were more likely to exhibit macroscopic evidence of VDD (45.5% females vs 30% males) but this was not statistically significant. Discussion and conclusions: Periods of poor mineral metabolism during childhood appear much more prevalent at Coach Lane than macroscopic evidence suggests. Evidence of seasonal IGD episodes indicates that northern latitude played a major role in poor VD status in the Northeast of England. The significant association of IGD with male sex may be due to sex-related differences in dentinal mineralization or a higher risk of poor VD status in males aged <5 years. More work is needed to establish an evidence-based threshold for pathological levels of IGD before the presence of this feature can confidently be used as a biomarker for poor VD status

Vitamin D status in post-medieval Northern England:Insights from dental histology and enamel peptide analysis at Coach Lane, North Shields (AD 1711-1857)

Objectives The post-medieval period in Europe saw a dramatic increase in metabolic bone disease related to vitamin D deficiency (VDD). Recent paleopathological work has utilized interglobular dentin (IGD) as a proxy for poor vitamin D status during development, while enamel peptide analysis allows the identification of chromosomal sex in non-adult remains. Here we explore the relationship between sex, the presence of IGD, and macroscopic markers of VDD in an industrial era assemblage from Northeast England. Materials and methods 25 individuals (9 females, 9 males, 9 unknown sex) from the cemetery site at Coach Lane, North Shields (1711-1857) were selected for paleopathological analysis, histological assessment of IGD, and enamel peptide determination of chromosomal sex. Results Ground tooth sections from 21 individuals were of suitable quality for detection of IGD, and enamel peptide analysis confirmed the chromosomal sex of ten individuals. Sixteen individuals (76.1%) exhibited ≥1 episode of IGD. Nine of these (42.8%) exhibited &gt;1 episode and four (19%) exhibited ≥4 episodes in regular intervals. Male sex was significantly associated with the presence of IGD (p = 0.0351; 100% males vs. 54.5% females). Females were more likely to exhibit macroscopic evidence of VDD (45.5% females vs 30% males) but this was not statistically significant. Discussion and conclusions Periods of poor mineral metabolism during childhood appear much more prevalent at Coach Lane than macroscopic evidence suggests. Evidence of seasonal IGD episodes indicates that northern latitude played a major role in poor VD status in the Northeast of England. The significant association of IGD with male sex may be due to sex-related differences in dentinal mineralization or a higher risk of poor VD status in males aged &lt;5 years. More work is needed to establish an evidence-based threshold for pathological levels of IGD before the presence of this feature can confidently be used as a biomarker for poor VD status.</p

Health benefi ts, costs, and cost-eff ectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost eff ective if the cost per DALY averted was less than the country’s 2012 per-head gross domestic product (GDP; South Africa:$8040; Zambia: $1425; India:$1489; Vietnam: $1407) and cost eff ective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from$237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to$749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost eff ective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to$241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost eff ective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost eff ective in lowincome and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets

Developing a typology for peer education and peer support delivered by prisoners

Peer interventions delivered for prisoners by prisoners offer a means to improve health and reduce risk factors for this population. The variety of peer programs poses challenges for synthesizing evidence. This paper presents a typology developed as part of a systematic review of peer interventions in prison settings. Peer interventions are grouped into four modes: peer education, peer support, peer mentoring and bridging roles, with the addition of a number of specific interventions identified through the review process. The paper discusses the different modes of peer delivery with reference to a wider health promotion literature on the value of social influence and support. In conclusion, the typology offers a framework for developing the evidence base across a diverse field of practice in correctional health care

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice

The work was supported by the Medical Research Council, U.K. (University of St Andrews Doctoral Training Grant to AV and CSA), Deutsche Forschungsgemeinschaft (PA 815/2-1) to CP, Tenovus Scotland (T15/38) to MN and Wellcome Trust to CP, MN (ISSF) and RER (101788/Z/13/Z)Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets. To exploit this, we have successfully developed and executed a novel modular cell-based platform that facilitates the safe and rapid screening for inhibitors of a viral IFN antagonist of choice. The platform is based on two reporter cell-lines that provide a simple method to detect activation of IFN induction or signaling via an eGFP gene placed under the control of the IFNβ or an ISRE-containing promoter, respectively. Expression of a target IFN antagonist in the appropriate reporter cell-line will block the IFN response and hence eGFP expression. We hypothesized that addition of a compound that inhibits IFN antagonist function will release the block imposed on the IFN response and hence restore eGFP expression, providing a measurable parameter for high throughput screening (HTS). We demonstrate assay proof-of-concept by (i) exploiting hepatitis C virus (HCV) protease inhibitors to inhibit NS3-4A's capacity to block IFN induction and (ii) successfully executing two HTS targeting viral IFN antagonists that block IFN signaling; NS2 and IE1 from human respiratory syncytial virus (RSV) and cytomegalovirus (CMV) respectively, two clinically important viruses for which vaccine development has thus far been unsuccessful and new antivirals are required. Both screens performed robustly and Z′ Factor scores of >0.6 were achieved. We identified (i) four hit compounds that specifically inhibit RSV NS2's ability to block IFN signaling by mediating STAT2 degradation and exhibit modest antiviral activity and (ii) two hit compounds that interfere with IE1 transcription and significantly impair CMV replication. Overall, we demonstrate assay proof-of-concept as we target viral IFN antagonists from unrelated viruses and demonstrate its suitability for HTS.Publisher PDFPeer reviewe