The relevance of false positive acid phosphatase reactions indicative of the presence of seminal fluid from oral and vaginal samples.

The Body Fluid Forum of the Association of Forensic Science Providers recognised concerns raised by forensic practitioners regarding the lack of data to inform on the incidence of significant AP (Acid Phosphatase) reactions from vaginal and oral samples, i.e. those which might be misinterpreted as indicating the presence of semen. This is particularly relevant in the light of appeal court rulings regarding the need for data to support evaluations. This paper presents collaborative data on the nature and incidence of AP reactions from vaginal and oral swabs provided by donors. The results demonstrate that caution is required with mid to strong purple AP reactions from direct testing of oral swabs and with mid purple reactions from vaginal swabs. The use of a Bayesian approach to assist with the provision of opinions regarding the presence of seminal fluid is highlighted.

Tropical Peatland Hydrology Simulated With a Global Land Surface Model.

Tropical peatlands are among the most carbon-dense ecosystems on Earth, and their water storage dynamics strongly control these carbon stocks. The hydrological functioning of tropical peatlands differs from that of northern peatlands, which has not yet been accounted for in global land surface models (LSMs). Here, we integrated tropical peat-specific hydrology modules into a global LSM for the first time, by utilizing the peatland-specific model structure adaptation (PEATCLSM) of the NASA Catchment Land Surface Model (CLSM). We developed literature-based parameter sets for natural (PEATCLSMTrop,Nat) and drained (PEATCLSMTrop,Drain) tropical peatlands. Simulations with PEATCLSMTrop,Nat were compared against those with the default CLSM version and the northern version of PEATCLSM (PEATCLSMNorth,Nat) with tropical vegetation input. All simulations were forced with global meteorological reanalysis input data for the major tropical peatland regions in Central and South America, the Congo Basin, and Southeast Asia. The evaluation against a unique and extensive data set of in situ water level and eddy covariance-derived evapotranspiration showed an overall improvement in bias and correlation compared to the default CLSM version. Over Southeast Asia, an additional simulation with PEATCLSMTrop,Drain was run to address the large fraction of drained tropical peatlands in this region. PEATCLSMTrop,Drain outperformed CLSM, PEATCLSMNorth,Nat, and PEATCLSMTrop,Nat over drained sites. Despite the overall improvements of PEATCLSMTrop,Nat over CLSM, there are strong differences in performance between the three study regions. We attribute these performance differences to regional differences in accuracy of meteorological forcing data, and differences in peatland hydrologic response that are not yet captured by our model.

Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

Prostaglandin E2 receptors and their role in gastrointestinal motility - Potential therapeutic targets.

Prostaglandin E2 (PGE2) is found throughout the gastrointestinal tract in a diverse variety of functions and roles. The recent discovery of four PGE2 receptor subtypes in intestinal muscle layers as well as in the enteric plexus has led to much interest in the study of their roles in gut motility. Gut dysmotility has been implicated in functional disease processes including irritable bowel syndrome (IBS) and slow transit constipation, and lubiprostone, a PGE2 derivative, has recently been licensed to treat both conditions. The diversity of actions of PGE2 in the intestinal tract is attributed to its differing effects on its downstream receptor types, as well as their varied distribution in the gut, in both health and disease. This review aims to identify the role and distribution of PGE2 receptors in the intestinal tract, and aims to elucidate their distinct role in gut motor function, with a specific focus on functional intestinal pathologies.

Alkali addition and roughage inclusion effect on performance and carcass characteristics of feedlot steers fed diets containing 60% dried distillers grains with solubles.

Three experiments were conducted to determine the effectiveness of calcium hydroxide (Ca(OH)2) addition and roughage inclusion on digestibility, performance, and carcass characteristics of steers fed 60% dried distillers grains with solubles (DGS). Statistical analyses for studies were conducted using the MIXED procedures of SAS. In experiment 1, 48 steers (353.5 ± 7.55 kg) were allotted to individual pens and fed 1 of 3 diets (dry matter [DM] basis) containing 60% dried DGS, 20% corn silage, and 4% supplement with: 1) 14.5% corn and no Ca(OH)2; 2) 14% corn and 2% Ca(OH)2; and 3) 14.5% additional corn silage and no Ca(OH)2. Steers fed Ca(OH)2 consumed the least (P = 0.03) and steers fed added corn silage consumed the most and had the least gain:feed (P = 0.02). Gain and carcass quality were not affected by treatment (P ≥ 0.48). In experiment 2, 112 steers (375.3 ± 19.25 kg) were allotted to pens (four pens per treatment; seven steers per pen) arranged as a 2 × 2 factorial (roughage × Ca(OH)2) and fed one of four diets (DM basis) containing 60% dried DGS, 17% corn silage, and 4% supplement with: 1) 17.5% corn silage and no Ca(OH)2; 2) 17% corn silage and 2% Ca(OH)2; 3) 17.25% corn stover and no Ca(OH)2; and 4) 17% corn stover and 2% Ca(OH)2. Added stover decreased average daily gain (ADG) compared to added corn silage (P = 0.04). Ca(OH)2 increased ADG when steers were fed stover, but not when steers were fed only corn silage (P = 0.05; interaction). In experiment 3, six ruminally cannulated steers (initial body weight = 352 ± 14.8 kg) were randomly allotted to a 6 × 6 Latin square design to determine the effects of roughage inclusion (corn, corn silage, stover) and Ca(OH)2 addition (0% or 2%) on ruminal characteristics. Feeding stover decreased total volatile fatty acid(s) (VFA) concentration and DM digestibility compared to corn silage or corn (P < 0.01), whereas Ca(OH)2 resulted in greater total VFA concentrations and DM digestibility (P ≤ 0.02). Stover increased rate of DM degradation (K d) and rate of particle outflow from the rumen (P ≤ 0.04) but decreased extent of DM digestion and mean retention time (P ≤ 0.02) compared to corn or silage. Ca(OH)2 increased K d (P < 0.01) and tended to increase (P = 0.06) liquid passage rate. In conclusion, added roughage did not improve performance of cattle fed 60% dried DGS. Ca(OH)2 may decrease intake and maintain performance of cattle fed 60% dried DGS with corn silage as the roughage source and increases ADG when corn stover replaces a portion of the corn silage.

Early Warning Scores do not accurately predict mortality in sepsis: A meta-analysis and systematic review of the literature.

OBJECTIVES: Early Warning Scores are used to evaluate patients in many hospital settings. It is not clear if these are accurate in predicting mortality in sepsis. We performed a systematic review and meta-analysis of multiple studies in sepsis. Our aim was to estimate the accuracy of EWS for mortality in this setting. METHODS: PubMED, CINAHL, Cochrane, Web of Science and EMBASE were searched to October 2016. Studies of adults with sepsis who had EWS calculated using any appropriate tool (e.g. NEWS, MEWS) were eligible for inclusion. Study quality was assessed using QUADAS-2. Summary estimates were derived using HSROC analysis. RESULTS: Six studies (4298 participants) were included. Results suggest that EWS cannot be used to predict which patients with sepsis will (positive likelihood ratio 1.79, 95% CI 1.53 to 2.11) or will not die (negative likelihood ratio 0.59, 95% CI 0.45 to 0.78). Two studies were rated as low risk of bias and one as unclear risk of bias on all domains. The other three studies were judged at high risk of bias in one domain. CONCLUSION: Early Warning Scores are not sufficiently accurate to rule in or rule out mortality in patients with sepsis, based on the evidence available, which is generally poor quality.

A phase I clinical trial demonstrates that nfP2X7 -targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma.

BACKGROUND: Expression of P2X7 , an ATP-gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X7 (termed nfP2X7 ), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers. OBJECTIVES: To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for basal cell carcinoma (BCC). METHODS: An open-label, phase I clinical trial was undertaken at three dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X7 antibodies (BIL010t) to primary BCC lesions twice daily for 28 days. Twenty-one patients with primary BCC lesions at least 0·5 cm2 in area and less than 2·0 cm in diameter were enrolled. The primary end points were safety, tolerability and pharmacokinetics. Change in lesion size after treatment was determined and histology was performed on pretreatment and end-of-treatment (EOT) biopsies. RESULTS: Compliance was very high, with treatment being well tolerated. The most common adverse events were treatment site erythema, pruritus, dryness and pain. There was no evidence of systemic penetration of the sheep antibody. Lesions were measured prior to and after 28 days of treatment, with 65% of patients showing a reduction in lesion area, 20% showing no change and 15% showing an increase. Histopathology of post-treatment excision of lesion sites showed eight patients with stable disease, nine with partial response and three with complete response. CONCLUSIONS: Antibodies against nfP2X7 (BIL010t) provide a novel, safe and well-tolerated treatment for BCC.

Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study).

BACKGROUND: Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland. AIM: To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22-year period. METHODS: Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014. RESULTS: There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria. CONCLUSIONS: The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria.

DNA transfer through nonintimate social contact.

The UK and Ireland Association of Forensic Science Providers' (AFSP) Body Fluid Forum (BFF) set out to assist in the interpretation of sexual offence cases where semen is absent on vaginal swabs but female DNA is present on penile swabs or male underwear, and the issue to be addressed is whether or not sexual intercourse occurred. This study aims to investigate the frequency and amount of female DNA transferred to the penis and underwear of males following staged nonintimate social contact with females and to compare the findings with the amount of female DNA transferred to the penis and subsequently to the underwear of a male who had engaged in unprotected sexual intercourse with a female. In this study, no matching female DNA was detected on the inside front of the 44 items of male underwear used in this research following staged contact of a nonintimate nature and subsequent secondary transfer to the penis. After sexual intercourse, full profiles matching the female participant were found on the inside front of the males underwear with maximum peak heights in the range between 1898 and 3157 rfu. It was possible to demonstrate that DNA can occasionally transfer to the waistband and outside front of underwear worn by a male following staged nonintimate social contact. Data obtained in this study suggest that a matching female DNA profile below a peak height of 1000 rfu on the waistband of a male's underwear might be explained by nonintimate social contact with secondary transfer of female DNA from the male's hands.

Blood metabolite markers of neocortical amyloid-ß burden: discovery and enrichment using candidate proteins.

We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti-amyloid trials.

Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor.

AIMS: Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa. MATERIALS AND METHODS: Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. KEY FINDINGS: PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. SIGNIFICANCE: The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease.

Assessing the bilateral geometrical differences of the tibia--are they the same?

Contralateral bones are often used in many medical applications but it is assumed that their bilateral differences are insignificant. Previous studies used a limited number of distance measurements in quantifying the corresponding differences; therefore, little is known about their bilateral 3D surface asymmetries. The aim of the study is to develop a comprehensive method to quantify geometrical asymmetries between the left and right tibia in order to provide first results on whether the contralateral tibia can be used as an equivalent reference. In this study, 3D bone models were reconstructed from CT scans of seven tibiae pairs, and 34 variables consisting of 2D and 3D measurements were measured from various anatomical regions. All 2D measurements, and lateral plateau and distal subchondral bone surface measurements showed insignificant differences (p>0.05), but the rest of the surfaces showed significant differences (p<0.05). Our results suggest that the contralateral tibia can be used as a reference especially in surgical applications such as articular reconstructions since the bilateral differences in the subchondral bone surfaces were less than 0.3mm. The method can also be potentially transferable to other relevant studies that require the accurate quantification of bone bilateral asymmetries.

Nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary Escherichia coli from US outpatients.

OBJECTIVES: To examine the prevalence of multidrug-resistant (MDR) urinary Escherichia coli among US outpatients and to assess the antimicrobial activity of oral antibiotics commonly used to treat urinary tract infections (UTIs) against MDR isolates. METHODS: Antimicrobial susceptibility testing data from outpatient urine cultures in The Surveillance Network (TSN) Database USA were analysed. Six antimicrobial agents from six separate drug classes were included: ampicillin, cefalotin, ciprofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole and amoxicillin/clavulanate. Isolates were categorized as resistant to one, two, three, four, five and six agents and compared for the years 2001 and 2010. Phenotypes of MDR isolates were assessed to determine antimicrobial activity of recommended therapy for UTIs. RESULTS: Prevalence of MDR E. coli increased from 9.1% in 2001 (n = 29,198) to 17.0% in 2010 (n = 32,742) (P < 0.0001). In isolates that demonstrated resistance to three, four or five antimicrobial agents in 2010, resistance to nitrofurantoin was observed in only 2.1%, 7.5% and 24.1% of isolates, respectively. Conversely, widespread resistance was observed for trimethoprim/sulfamethoxazole (62.6%, 88.6% and 97.9% for isolates resistant to three, four and five agents, respectively) and ciprofloxacin (48.9%, 84.3% and 98.2% for isolates resistant to three, four and five agents, respectively). CONCLUSIONS: Because of its consistent antimicrobial activity against MDR E. coli, nitrofurantoin remains a reliable first-line agent for the empirical treatment of acute uncomplicated cystitis.

Genome-wide association study identifies genomic regions of association for cruciate ligament rupture in Newfoundland dogs.

Cranial cruciate ligament rupture (CCLR) is the most common cause of pelvic limb lameness in dogs. To investigate the genetic basis of canine CCLR, we conducted a genome-wide association study using a canine SNP array in Newfoundland pedigree dogs with and without CCLR (n = 96). We identified three main chromosomal regions of CCLR association (on chromosomes 1, 3 and 33). Each of these regions was confirmed by Sequenom genotyping in a further cohort of Newfoundlands (n = 271). The results, particularly SNPs identified in the SORCS2 and SEMA5B genes, suggest that there may be neurological pathways involved in susceptibility to canine CCLR.

Guidelines: is bigger better? A review of SIGN guidelines.

OBJECTIVES: To quantify and analyse the quality of evidence that is presented in national guidelines. SETTING: Levels of evidence used in all the current valid recommendations in the Scottish Intercollegiate Guideline Network (SIGN) guidelines were reviewed and statistically analysed. OUTCOME MEASURES: The proportion of level D evidence used in each guideline and a statistical analysis. METHOD: Data were collected from published guidelines available online to the public. SIGN methodology entails a professional group selected by a national organisation to develop each of these guidelines. Statistical analysis of the relationship between the number of guideline recommendations and the quality of evidence used in its recommendations was performed. RESULT: The proportion of level D evidence increases with the number of recommendations made. This correlation is significant with Kendall's τ=0.22 (approximate 95% CI 0.008 to 0.45), p = 0.04; and Spearman ρ=0.22 (approximate 95% CI 0.02 to 0.57), p=0.04. CONCLUSIONS: Practice guidelines should be brief and based on scientific evidence. Paradoxically the longest guidelines have the highest proportion of recommendations based on the lowest level of evidence. Guideline developers should be more aware of the need for brevity and a stricter application of evidence-based principles could achieve this. The findings support calls for a review of how evidence is used and presented in guidelines.