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Sensing of nutrients by chemosensory cells in the gastrointestinal tract plays a key role in transmitting food-related signals, linking information about the composition of ingested foods to digestive processes. In recent years, a number of G protein-coupled receptors (GPCR) responsive to a range of nutrients have been identified. Many are localised to intestinal enteroendocrine (chemosensory) cells, promoting hormonal and neuronal signalling locally, centrally and to the periphery. The field of gut sensory systems is relatively new and still evolving. Despite huge interest in these nutrient-sensing GPCR, both as sensors for nutritional status and targets for preventing the development of metabolic diseases, major challenges remain to be resolved. However, the gut expressed sweet taste receptor, resident in L-enteroendocrine cells and responsive to dietary sweetener additives, has already been successfully explored and utilised as a therapeutic target, treating weaning-related disorders in young animals. In addition to sensing nutrients, many GPCR are targets for drugs used in clinical practice. As such these receptors, in particular those expressed in L-cells, are currently being assessed as potential new pathways for treating diabetes and obesity. Furthermore, growing recognition of gut chemosensing of microbial-produced SCFA acids has led further attention to the association between nutrition and development of chronic disorders focusing on the relationship between nutrients, gut microbiota and health. The central importance of gut nutrient sensing in the control of gastrointestinal physiology, health promotion and gut-brain communication offers promise that further therapeutic successes and nutritional recommendations will arise from research in this area.

Background: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD)., Methods: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted., Results: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones., Conclusion: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Colloid-facilitated transport can be important for preferential transfer of phosphorus (P) through the soil profile to groundwater and may in part explain elevated P concentrations in surface water during baseflow and particularly high flow conditions. To investigate the potential for colloidal P (P coll ) mobilisation in soils, this study assessed the role of soil chemical properties and P fertilizer type on medium-sized soil P coll (200-450 nm) and its association with soil solution soluble bioavailable P (<450 nm). Hillslope soils from three agricultural catchments were sampled and untreated and treated (cattle slurry and synthetic fertilizer) subsamples were incubated. Soil supernatants were analysed for P and soil Water Dispersible Colloids (WDC) were extracted for analysis of P and P-binding materials. Soils physicochemical properties including degree of P saturation (DPS) and P sorption properties were determined. Results indicated that medium-sized P coll was mostly unreactive P associated to some extent to amorphous forms of Fe. Medium-sized P coll concentrations correlated negatively with soil maximum P sorption capacity and soluble P concentrations increased with increasing DPS. In soil with low sorption properties, cattle slurry increased soluble P concentrations by 0.008-0.013 mg l -1 and DPS but did not influence medium-sized P coll . Synthetic fertilizer increased medium-sized reactive P coll by 0.011 mg l -1 (0.088 mg kg -1 soil) and DPS in a soil with lower DPS whereas it decreased it by 0.005 mg l -1 (0.040 mg kg -1 soil) in a soil with higher DPS. Additional soil parameters (M3-Fe, M3-Al, M3-P, and DPS) should be included in soil testing, especially in Cambisol/Podzol soils, to identify critical areas where risks of P coll mobilisation are important. Further research should include the roles of finer colloidal and nanoparticulate (<200 nm) soil P fractions and soluble P to inform understanding of plant uptake and assess environmental risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Although transitional care interventions can improve health among patients hospitalized with acute conditions, few interventions use patient quality of life (QOL) as the primary outcome. Existing interventions use a variety of intervention components, are not effective for patients of all races and ethnicities, do not address age-related patient needs, and do not incorporate the needs of families. The purpose of this study was to systematically review characteristics of transitional care intervention studies that aimed to improve QOL for younger adult patients of all race and ethnicities who were hospitalized with acute conditions., Methods: A systematic review was conducted of empirical literature available in PubMed, Embase, CINAHL, and PsycINFO by November 19, 2019 to identify studies of hospital to home care transitions with QOL as the primary outcome. Data extraction on study design and intervention components was limited to studies of patients aged 18-64., Results: Nineteen articles comprising 17 studies met inclusion criteria. There were a total of 3,122 patients across all studies (range: 28-536). Populations of focus included cardiovascular disease, chronic obstructive pulmonary disease, stroke, breast cancer, and kidney disease. Seven QOL instruments were identified. All interventions were multi-component with a total of 31 different strategies used. Most interventions were facilitated by a registered nurse. Seven studies discussed intervention facilitator training and eight discussed intervention materials utilized. No studies specified cultural tailoring of interventions or analyzed findings by racial/ethnic subgroup., Conclusions: Future research is needed to determine which intervention components, either in isolation or in combination, are effective in improving QOL. Future studies should also elaborate on the background and training of intervention facilitators and on materials utilized and may also consider incorporating differences in culture, race and ethnicity into all phases of the research process in an effort to address and reduce any health disparities.

The perception of sweet is mediated by the sweet taste receptor T1R2-T1R3 expressed in taste cells of the lingual epithelium. This receptor is also expressed in intestinal enteroendocrine cells and is required for sensing luminal sugars and sweeteners to regulate expression of intestinal Na + -glucose cotransporter 1 (SGLT1). There are some notable differences amongst species in the ability to detect certain non-nutritive (artificial) sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes are responsible for these disparities. Using heterologous expression, we demonstrate that the commonly used non-nutritive sweeteners sucralose, saccharin and acesulfame K activate pig T1R2-T1R3, but that aspartame and cyclamate do not. Furthermore, we show that in vitro sweetener activation of pig T1R2-T1R3 mirrors the sweetener stimulation of the gut-expressed receptor in vivo. Considering that sweeteners are included in animal feed worldwide, determination of taste receptor specificities in different species is essential for the development of scientifically-based dietary formulations., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The ability to manipulate chromosomally encoded genes is a fundamental biological tool for the analysis of gene function. Here, we provide in greater depth a protocol for the creation of nonpolar unlabelled gene deletions in Listeria monocytogenes that are facilitated by the splicing overlap extension PCR technique. For mutagenesis in L. monocytogenes, we describe the pKSV7 plasmid-based approach, which facilitates the introduction of a spliced amplicon in place of the corresponding segment of chromosomal DNA.

Introduction: For many training programs, including hematology, there are limited structured opportunities to practice collaboration as a competency. Training is often limited to ad hoc interactions during clinical rotations. Accordingly, there is further need for immersive and standardized collaboration educational programs. This pilot study explored simulation for developing and assessing collaboration competency among hematology residents., Methods: Two standardized simulation center scenarios were developed that required residents to work in interprofessional teams. The objectives were to develop collaboration competence and confidence through experiential learning and facilitated reflection. Team members included education and simulation experts as well as hematology nurses as embedded participants. Case 1 presented a 72-year-old male with stage 4 lymphoma experiencing shortness of breath during a rituximab infusion. Case 2 presented a 68-year-old male who suffered a provoked pulmonary embolism. Both cases utilized a simulated clinic space. Pre, post, and 3-month questionnaires (self-assessed collaboration competency and simulation evaluation) were completed. Each session included structured debriefing with facilitated reflection focused on collaboration., Results: Seven senior hematology subspecialty residents participated. Despite residents entering the simulation cases with confidence in collaboration, higher collaboration confidence ratings were observed on postsimulation questionnaires (8.2 vs. 7.6 on a 10-point Likert scale). Residents demonstrated awareness of appropriate collaboration skills, but at times failed to implement knowledge into action. Facilitated reflection during the debrief helped residents critique their collaboration performance and develop improvement plans., Discussion: Simulation is a promising tool for teaching and assessing collaboration within hematology training., (© 2020 Liederman et al.)

Background: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe., Methods: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries ( n =13) from middle-income countries ( n =14)., Results: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p =0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries., Conclusion: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Although cells of mushroom-producing fungi typically contain paired haploid nuclei (n + n), most Armillaria gallica vegetative cells are uninucleate. As vegetative nuclei are produced by fusions of paired haploid nuclei, they are thought to be diploid (2n). Here we report finding haploid vegetative nuclei in A. gallica at multiple sites in southeastern Massachusetts, USA. Sequencing multiple clones of a single-copy gene isolated from single hyphal filaments revealed nuclear heterogeneity both among and within hyphae. Cytoplasmic bridges connected hyphae in field-collected and cultured samples, and we propose nuclear migration through bridges maintains this nuclear heterogeneity. Growth studies demonstrate among- and within-hypha phenotypic variation for growth in response to gallic acid, a plant-produced antifungal compound. The existence of both genetic and phenotypic variation within vegetative hyphae suggests that fungal individuals have the potential to evolve within a single generation in response to environmental variation over time and space.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes . The following article describes the design and implementation of a pharmacist-led program to improve rates of statin use among appropriate patients in high-risk populations., (© 2020 by the American Diabetes Association.)

In China, excessive phosphorus (P) application in protected vegetable fields has led to high legacy P stores. Soil amendment with alum or dolomite is one of many best management practices (BMPs) used to reduce P losses in calcareous soils. However, both the kinetics and mechanisms of P sorption and soil available P in amended soils are understudied. Herein, both aspects were looked at under controlled conditions. Firstly, a sorption study which coupled P concentrations with poorly-crystalline Al hydroxides and dolomite was conducted. Results from this batch experiment showed that P sorption on poorly-crystalline Al hydroxides was homogenous and occurred mainly via displacement of inner-sphere hydroxyl (Al-OH) instead of the formation of AlPO 4 . However, the amount of sorbed P reached maximum sorption of 73.1 mg g -1 and did not change with further increase in P concentration. It was observed that P adsorbed onto the dolomite surface at low P concentrations, whereas hydroxyl replacement and uneven cluster precipitation of Ca 3 (PO 4 ) 2 occurred at high P concentrations. A second 90 day incubation experiment investigated changes to soil available P and sorption-desorption across variable rates of amendments (0-50 g kg -1 ). Results showed that alum amendment at a rate of 50 g kg -1 decreased soil CaCl 2 -P and Olsen-P concentrations by 91.9% and 57.8%, respectively. However, Olsen-P increased when the dolomite rates were <20 g kg -1 . Phosphorus sorption-desorption of the amended soil showed alum had higher P sorption efficiency than dolomite at low addition rates (<10 g kg -1 ). However, soil amended with high dolomite rates (>10 g kg -1 ) could sorb more P in comparison with alum when P concentrations were increased. The P status of the amended soil was closely connected to the P sorption mechanisms on mineral amendments, soil P concentrations and soil properties., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Consequences of prescription opioid use involve harms, addiction, tolerance and death. Despite routine prescription, opioids are not recommended for initial intervention by any major multidisciplinary low back pain (LBP) guideline., Objective: Our primary purpose was to improve overall understanding of the harms and benefits associated with oral opioid interventions prescribed for treatment of acute or chronic back pain. Our second goal was to evaluate pain intensity and to compare and contrast these data with the harms. Our last objective was to evaluate conflicts of interest among the study authors and the findings., Design/data/eligibility Criteria: Studies incorporating oral prescription opioid management of non-surgical LBP were evaluated. After systematic assessment, no studies that met inclusion included participants with specifically acute LBP. Therefore, extracted data reflects only populations with subacute and chronic LBP. Data on reported harms, severe harms, pain outcomes and withdrawal rates were extracted and meta-analyses were completed for opioid versus placebo trials and opioids versus non-opioid trials., Results: Fourteen studies met inclusion/exclusion requirements. All trials involved short-term management with limited follow-up. A high percentage of harms were identified across most studies. Opioids were not shown to be superior to other medications, and only showed superiority to placebo comparators (at cost of additional harms)., Conclusion: This review identified trends of higher harms rates and higher percentages of severe harms in opioid arms for the management of subacute and chronic LBP. The majority of trials that demonstrated benefits with opioids also had potential conflicts of interest. Lastly, non-opioid medications demonstrated statistically significant pain improvement compared with opioids. We feel that the results of the trial are supportive of current LBP guidelines and do not condone the initial use of opioids in management of subacute or chronic LBP., Trial Registration Number: CRD42017070914., Competing Interests: Competing interests: CEC receives royalties from Book sales and educational material. CEC is a paid editor for JOSPT. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Toll-like receptors (TLRs) play a key role in the recognition of microbes via detection of specific and conserved microbial molecular features. TLRs, mainly expressed in immune cells, interact with intestinal microbiome. Little is known about mechanism(s) of sensing of bacteria by the intestinal surface enteroendocrine cells (EECs). We show here that TLR9 is expressed by the EECs of proximal intestine in a range of species and is co-expressed with the satiety hormone cholecystokinin (CCK). CCK secreted in excess induces emesis (vomiting). Using an EEC model cell line, STC-1, we demonstrate that in response to the TLR9 agonist, DNA containing unmethylated CpG dinucleotide motifs, STC-1 cells secrete CCK and that this secretion is inhibited by specific inhibitors of TLR9. Exposure of STC-1 cells to heat-inactivated pathogenic bacteria, Escherichia coli O55/H7, Shigella flexneri 2457T, Salmonella typhimurium ST4/74, and non-pathogenic Lactobacillus amylovorus GRL1112, results to an increase in CCK secretion compared to untreated control. The magnitudes of CCK release are higher in response to pathogenic bacteria and lowest in response to the non-pathogenic L. amylovorus. The pathogenic strains not only have substantially bigger genomes than L. amylovorus, they also have significantly higher numbers/frequency of RR/CG/YY stimulatory CpG hexamers in their genomic DNA. Pathogen-induced excessive secretion of the gut hormone CCK, provoking emesis can serve as a protective mechanism against development of enteric infections., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Agricultural drainage systems comprising both in-field pipe drains and surface ditches are typically installed to remove excess water from agricultural land. These drainage networks can provide connectivity between phosphorus (P) sources and surface waters thereby increasing the risk of P loss to rivers and streams. The objective of this study was to derive a farm-scale drainage ranking that categorises drainage ditches in terms of P loss risk based on connectivity and physic-chemical characteristics. Ten pilot farms were selected to characterise drainage networks through ground survey and, sediment and water sampling. Five drainage ditch categories were derived based on landscape setting and connectivity. Each category recorded soluble and reactive P concentrations above environmental water quality standards. To assess the risk of surface ditches as a connectivity vector between agricultural P and surface waters ditches were ranked in order of P loss risk by integrating landscape position and sediment P chemistry. Elevated sediment P with high equilibrium P concentration (EPCo) were associated with ditches connected to farm yards, and in sediment sampled at ditch outlets, suggesting P deposition over time indicative of a legacy P source. The greatest risk of P loss was attributed to ditches connecting farm yards to streams, and ditches that connected the drainage network to surface waters, or Outlets. These results rank connectivity risk for P loss along agricultural drainage ditches for farm level risk assessment to target P loss mitigation measures to the appropriate locations., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Health workers (HWs) are increasingly using mobile health (mHealth) technologies in low-resource settings. Understanding HW acceptability of mHealth is critical to increasing the scale of mHealth solutions. We examined pre- and post-pilot clinical knowledge and acceptability of a tablet-based platform, the Tanzania Health Information System (T-HIT), targeting HWs delivering prevention of mother-to-child transmission (PMTCT) of HIV services in seven health facilities in Misungwi District, Tanzania., Methods: We developed a survey based on the diffusion of innovation theory and administered it to 27 HWs before and after a 3-month pilot of T-HIT. Using a Wilcoxon signed-rank test, we analyzed changes in acceptability defined as attitudes towards and self-efficacy for system use comparing pre- and post-test assessment scores and changes in knowledge of clinical care. Using analysis of variance, we explored these changes, stratifying health facilities by level of care and by distance from the district hospital., Results: Post-pilot scores showed statistically significant improvement from pre-test for the total survey ( Z  = -2.67, p  < 0.008) and for questions concerning system attitude ( Z  = -2.63, p  < 0.008). HWs in hospitals and health centers exhibited a lower initial level of system acceptability in attitude than those in dispensaries and a significant improvement in overall mean acceptability over the pilot (95% CI 0.004-0.0187). HWs working more than 20 km from the hospital had a lower initial level of both system knowledge and acceptability than their less remote counterparts, but demonstrated larger improvements in knowledge and acceptability over time, although this change was not statistically significant., Conclusions: The pilot demonstrates that HWs in PMTCT in Misungwi have a high acceptability of mHealth solutions. Using an mHealth solution can facilitate HW delivery of PMTCT care in rural and remote settings. Consideration of acceptability is important for fostering mHealth scale and program sustainability., (© The Author(s) 2020.)

Absorption of glucose, via intestinal Na + /glucose cotransporter 1 (SGLT1), activates salt and water absorption and is an effective route for treating Escherichia coli ( E. coli )-induced diarrhea. Activity and expression of SGLT1 is regulated by sensing of sugars and artificial/natural sweeteners by the intestinal sweet receptor T1R2-T1R3 expressed in enteroendocrine cells. Diarrhea, caused by the bacterial pathogen E. coli , is the most common post-weaning clinical feature in rabbits, leading to mortality. We demonstrate here that, in rabbits with experimentally E. coli -induced diarrhea, inclusion of a supplement containing stevia leaf extract (SL) in the feed decreases cumulative morbidity, improving clinical signs of disease ( p < 0.01). We show that the rabbit intestine expresses T1R2-T1R3. Furthermore, intake of SL enhances activity and expression of SGLT1 and the intestinal capacity to absorb glucose (1.8-fold increase, p < 0.05). Thus, a natural plant extract sweetener can act as an effective feed additive for lessening the negative impact of enteric diseases in animals.

Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a methyl substitution ortho to the heteroaryl groups on an aniline core significantly improved the potency of this series of compounds. These findings predated the availability of SMO crystal structure in 2013. Here we retrospectively applied quantum mechanics calculations to demonstrate the o-Me substitution favors the bioactive conformation by inducing a dihedral twist between the heteroaryl rings and the core aniline. The o-Me also makes favorable hydrophobic interactions with key residue side chains in the binding pocket. From this effort, two compounds (AZD8542 and AZD7254) showed excellent pharmacokinetics across multiple preclinical species and demonstrated in vivo activity in abrogating the Hh paracrine pathway as well as anti- tumor effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Cytomegalovirus (CMV) is the most common congenital infection and can cause hearing loss and neurodevelopmental disability in infected infants. International research shows women have limited knowledge about CMV., Aims: To assess pregnant women's knowledge and attitudes about CMV before and after provision of information., Materials and Methods: Cross-sectional survey of pregnant women between November 2017 and February 2018 at two Australian hospitals. Participating women completed an initial survey on maternal characteristics, knowledge of infections, and CMV risk behaviours. Participants were then given an information leaflet and completed a follow-up survey., Results: Four hundred and fifty-seven women completed the initial survey, of whom 73/457 (16%) had heard of CMV. Behaviours increasing risk of CMV transmission were common: 58% reported regularly kissing their child on the lips; 57% did not always wash their hands after changing a wet nappy. Knowledge about CMV significantly improved after reading the leaflet in the 145 women completing the follow-up survey. More women correctly identified that CMV could cause deafness in a baby (35% before, 85% after), was spread by saliva (38% vs 94%) or urine (27% vs 86%) and prevented by hand-washing (55% vs 99%; all P < 0.001)., Conclusion: Knowledge about CMV was low in pregnant women. An educational leaflet was effective in improving knowledge., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Carcinoma of unknown primary represents a therapeutic challenge in oncological practice. Evidence lacks to support particular chemotherapy selection and empirical therapies are commonly extrapolated from data on patients where primary tumor site is known. Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil was previously developed to treat pancreatic cancer. These agents have also demonstrated activities in other gastrointestinal malignancies. Considering promising anti-tumor effects of GOLF, we performed a retrospective study to investigate anti-tumor activity and safety of a simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil in patients with Carcinoma of unknown primary in whom immunohistostaining was suggestive of either upper gastrointestinal cancers or pancreatobiliary cancers., Methods: This retrospective study included 18 patients recorded to have a diagnosis of Carcinoma of unknown primary between Aug 2010-Dec 2015, who received biweekly G 1000 mg/m 2 , O 85 mg/m 2 , L 200 mg/m 2 and F 2400 mg/m 2 over 46-h on day 1 with pegfilgrastim on day 3 every 14 days. IHC staining pattern favored upper GI origin, including stomach, bile duct or pancreas. Tumor assessments were repeated every 8 weeks., Results: Median age was 67 years (range: 46-76), with ECOG PS<2, and 50% were women. Median number of cycles was 4 (range: 3-14). 7 partial responses were obtained (RR: 39%) and 7 achieved stable disease with overall disease control of 78%. Median time to tumor progression was 4 months (range: 2-9). 8 (44%) patients received liver-directed therapy and 1 underwent HIPEC (5%). Median survival time was 10.5 months (range: 6.7-14.5) and 1-year overall survival rate was 35%. Grade 3-4 toxicities included neutropenia, febrile neutropenia, thrombocytopenia, nausea, diarrhea, mucositis and oxaliplatin-induced neuropathy., Conclusion: Simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil regimen appears to be feasible with promising activity for Carcinoma of unknown primary and deserves to be evaluated in future trials., Competing Interests: Conflicts of Interest The authors report no conflict of interest.

The impact of dietary composition and prebiotics, in promoting the growth of beneficial groups of gut bacteria, is increasingly apparent. Using Illumina MiSeq sequencing of bacterial 16S rRNA genes, this study has aimed to characterize and compare the establishment of the gastrointestinal microbiota in dairy calves given two different commercial milk replacer (MR) diets. MR1 and MR2 contain different levels of macronutrients such as protein and fat. Moreover, differences in manufacturing methods infer that MR2 may contain a greater proportion of conjugated milk oligosaccharides (OS), while MR1 contains more free milk OS. A total of 10 dairy calves, five in each group, were assigned to one of the two MR diets. Freshly voided fecal samples were taken at 0, 7, 14, 28, and 49 days after first consumption of milk replacer. The relative abundance of two individual Bifidobacterium species, which are known to utilize milk OS, and Faecalibacterium prausnitzii were significantly higher at day 7 in the fecal microbiome of calves fed MR2 compared with MR1. These commensal bacteria are widely regarded as probiotic organisms that confer a health benefit on the host. Our findings suggest that the composition of bovine milk replacers can have significant effects on the establishment of the gut microbiota in pre-weaned (neonatal) dairy calves. Better understanding of milk composition-microbiota-host interactions in early life will inform targeted interventions to increase growth and reduce mortality in young animals., (Copyright © 2019 Badman, Daly, Kelly, Moran, Cameron, Watson, Newbold and Shirazi-Beechey.)

Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation ( n = 51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4 + and CD8 + T cell populations are highly activated in both compartments, with CD4 + T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA.

Current policy instruments under the EU Water Framework Directive (WFD) to mitigate phosphorus (P) loss require that P use on farms is managed through regulation of farm gate P balances. Regulation at farm scale does not account for spatial variability in nutrient use and soil fertility at field scale, affecting the costs and effectiveness of farm gate measures. This study simulated the implementation of a P loss mitigation measure coupled with improving soil fertility so that farm productivity would not be compromised. The measure was simulated at field scale and the costs and effectiveness assessed at farm scale. Effectiveness was expressed as the time taken for excessive soil P levels to decline to levels that matched off-takes and this varied temporally and spatially within and between farms ranging from 1 to 8 years. Sub-optimum soil fertility was corrected on all fields across both farms, with applications of other soil nutrients and lime to protect productivity. An increase in costs ranging from 1.5 to 116% was predicted in the first two years of the measure on both farms after-which savings of 15-31% were predicted for each subsequent year until the measure was effective in year 9. Despite initial cost increase, there was no statistically significant difference in costs over the time taken for the measure to be effective, when compared to baseline costs. Successful implementation of measures should consider the impact on farm costs and time taken for measures to environmentally effective. Adoption of measures could improve if demonstrating to farmers that costs will not vary significantly from current practice and in time may results in savings if measures are paired with correcting soil fertility and increasing yields. This 'win-win' approach could be used into the future to ensure successful implementation and uptake of measures within the farming community., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

From an environmental perspective optimised dairy systems, which follow current regulations, still have low nitrogen (N) use efficiency, high N surplus (kg N ha-1) and enable ad-hoc delivery of direct and indirect reactive N losses to water and the atmosphere. The objective of the present study was to divide an intensive dairy farm into N attenuation capacity areas based on this ad-hoc delivery. Historical and current spatial and temporal multi-level datasets (stable isotope and dissolved gas) were combined and interpreted. Results showed that the farm had four distinct attenuation areas: high N attenuation: characterised by ammonium-N (NH4+-N) below 0.23 mg NH4+-N l-1 and nitrate (NO3--N) below 5.65 mg NO3--N l-1 in surface, drainage and groundwater, located on imperfectly to moderately-well drained soils with high denitrification potential and low nitrous oxide (N2O) emissions (av. 0.0032 mg N2O-N l-1); moderate N attenuation: characterised by low NO3--N concentration in drainage water but high N2O production (0.0317 mg N2O-N l-1) and denitrification potential lower than group 1 (av. δ15N-NO3-: 16.4‰, av. δ18O-NO3-: 9.2‰), on well to moderately drained soils; low N attenuation-area 1: characterised by high NO3--N (av. 6.90 mg NO3--N l-1) in drainage water from well to moderately-well drained soils, with low denitrification potential (av. δ15N-NO3-: 9.5‰, av. δ18O-NO3-: 5.9‰) and high N2O emissions (0.0319 mg N2O l-1); and low N attenuation-area 2: characterised by high NH4+-N (av. 3.93 mg NH4+-N l-1 and high N2O emissions (av. 0.0521 mg N2O l-1) from well to imperfectly drained soil. N loads on site should be moved away from low attenuation areas and emissions to air and water should be assessed., Competing Interests: The authors have declared that no competing interests exist.

Fish production is increasingly important to global food security. A major factor in maintaining health, productivity and welfare of farmed fish is the establishment and promotion of a stable and beneficial intestinal microbiota. Understanding the effects of factors such as host and environment on gut microbial community structure is essential for developing strategies for stimulating the establishment of a health-promoting gut-microbiota. We compared intestinal microbiota of common carp and rainbow trout, two fish with different dietary habits, sourced from various farm locations. There were distinct differences in the gut microbiota of carp and trout intestine. The microbiota of carp was dominated by Fusobacteriia and Gammaproteobacteria, while the trout microbiota consisted predominantly of Mollicutes and Betaproteobacteria. The majority of bacterial sequences clustered into a relatively low number of operational taxonomic units (OTUs) revealing a comparatively simple microbiota, with Cetobacterium, Aeromonas and Mycoplasma being highly abundant. Within each species, fish from different facilities were found to have markedly similar predominant bacterial populations despite distinctly different rearing environments, demonstrating intra-species uniformity and significant influence of host selectivity. This study demonstrates that in fish the host species imparts substantial impact in shaping the community structure of the intestinal microbiota.

Organic soils have low sorption capacities for phosphorus (P), and may pose a risk of P loss to water if P applications to these soils coincide with runoff events. Little is known about the magnitude of exports of P in overland flow following application of P fertiliser onto these soils, or on the influence of the frequency on P losses and persistence. The number of P fertiliser applications was surveyed across 39 commercial farms to assess current practice and inform the design of a rainfall runoff experiment to evaluate the effect of frequency of P applications on losses and persistence across time. Superphosphate (16% P) was applied in single (equivalent to 30 and 55 kg P ha -1 applied at day 0) and split (equivalent to 15 and 27.5 kg P ha -1 applied in two doses at days 0 and 55) applications to an organic soil inclined at a slope of 6% in a rainfall simulator experiment. The surface runoff of dissolved reactive phosphorus (DRP) was measured in controlled 30-min rainfall simulations conducted intermittently over an 85-day period. The DRP losses in surface runoff after the first rainfall event were 44.6 and 97.8 mg L -1 for single applications of 30 and 55 kg ha -1 , respectively, and 13.3 and 21.8 mg L -1 for the same rates split in two doses, indicating that single P applications had disproportionately bigger impacts on losses than split applications. This supports the idea that frequent, but smaller, P applications can minimise the impact of fertilisation on waters. Dissolved reactive P concentrations remained significantly higher than those from the control samples until the end the experiment for almost all the P treatments, highlighting the long-lasting effects of added P and the elevated risk of P losses on organic soils. For climates with frequent rainfall events, which are likely to coincide with fertiliser applications, smaller but more frequent P applications can reduce the risk of P transfer as opposed to one single application., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This article was migrated. The article was marked as recommended. Objective: To examine medical students' engagement in wellness activities and evaluate the effects of biofeedback and structured napping on measures of stress, burnout and wellbeing. Method: A randomized trial of heart-rate variability (HRV) biofeedback and structured napping used by pre-clinical medical students at the University of Central Florida College of Medicine compared with a control group was conducted. Baseline measurement occurred in August 2016 with the follow-up period in March 2017. To measure biofeedback, participants used Heartmath Biofeedback® with Inner Balance® software to record HRV measurements while they engaged in self-guided breathing three times weekly. The biofeedback device connected to participants' iPhone or iPad with a sensor that clipped to users' earlobes. HRV recordings were stored in a heart-cloud database, and participants had the option to share their recordings with the researchers. Participants used sleep pods (MetroNaps Energy Pods®) to engage in 20-minute structured naps three times weekly. Participants completed six psychosocial self-report questionnaires at baseline (T1) and two follow-up points (T2, T3). The questionnaires included the Interpersonal Reactivity Index; Perceived Stress Scale; Quality of life scale; Oldenburg Burnout Inventory; and the Physician Well-Being Index. Results: Forty-two students enrolled in the study. Throughout the study, participants recorded 276 structured naps lasting approximately 20 minutes in duration and shared 24 personalized biofeedback recordings. Conclusions: Promotion of structured napping offers promise as an institution-initiated wellness intervention to promote medical students' mental health and wellbeing. HRV biofeedback warrants further study given the lack of conclusive findings in this study., (Copyright: © 2019 Hernandez C et al.)

Surplus phosphorus (P) above agronomic requirements can negatively affect the water status of connected surface and subsurface water bodies. The in situ stabilization of soil P through soil amendment has been recognized as an efficient way to reduce this environmental pressure. However, the mechanism of how P is stabilized during this process and how plant available P is affected are unknown. This can be achieved by sequential chemical extraction and synchrotron-based X-ray absorption near-edge structure (XANES) spectroscopy investigations. Therefore, in the present study, P-enriched calcareous and red soils were amended with alum, dolomite, and a 1:1 mixture of alum and dolomite (MAD) at a 20 g/kg soil rate, and soil properties and P fractions were measured after a 45-day period. Results showed that alum amendment significantly decreased CaCl 2 -P and Olsen-P contents in calcareous and red soils when compared with dolomite. However, dolomite incorporation maintained relatively high P availability and even increased CaCl 2 -P and Olsen-P contents by 1.32% and 40.5% in red soil, respectively, compared to control. Amendment with MAD was not as effectively as the alum in P stabilization. Sequential inorganic P extraction indicated that alum dominantly contributed labile P transformed to Al-P in both soils. P K-edge XANES spectroscopy measurements further explained that alum adsorbed phosphate in calcareous soil and precipitated phosphate as AlPO 4 in red soil. Results of P fractionation and Mehlich-3-extracted Ca showed that dolomite mainly adsorbed loosely bound P in calcareous soil and red soil. However, dolomite incorporation in red soil led to Al-P and Fe-P release. The P sorption isotherms showed that dolomite and alum increased soil P sorption maxima and decreased the degree of P saturation (DPS) in both soils, while dolomite declined the Langmuir bonding energy in red soil. Differences in P stabilization by alum and dolomite addition across soil types were closely related to their characteristics, and soil properties changed, especially soil pH.

A special course on Marriage, the Family and Human Sexuality was established at Kenrick-Glennon Seminary in St. Louis so as to assist the seminarians in their better understanding of the Church's teaching relative to natural methods of family planning and women's health care. This article compares the response at the beginning of this three-credit semester course to the same seven-item questionnaire given at the conclusion of the course. The pre- and postcourse scores were calculated for each of the questions. The scores obtained after the course were all significantly higher than they were before the course with p values ranging from 0.01 to <0.0001. Four of the items showed marked improvement including an understanding of the church's teaching related to natural methods, current methods of natural family planning, the impact of a natural method on a couple's marriage, and also the impact of a natural method on family life. Statistically significant improvement was also seen in their understanding of the topic of natural family planning and the Creighton Model System and its relevance toward the seminarian's vocation, the use of the methods to either achieve or avoid pregnancy, and how contraception and abortion are linked. In these last three items, the level of statistical significance was quite high, although not as high as the other four items. There were 104 seminarians over an eight-year period of time, who provided answers to these questions, both before and after the course. This course was modeled after a course that was initiated at the Pope Paul VI Institute for the Study of Human Reproduction, which was for priests, seminarians, and Catholic leaders, titled Love & Life Unlimited., Nontechnical Summary: This is an evaluation of a ten-point, seven-question questionnaire that was utilized at the beginning of a course at Kenrick Seminary in Marriage, Sexuality, Creighton Model and NaProTECHNOLOGY. The same questionnaire was given to the students at the beginning of the course and then two to three months later at the conclusion of the three-credit course. The results show that there is a significant improvement in the seminarians' knowledge and general attitude about natural methods of family planning and suggests that such courses would be beneficial to establish in seminaries throughout the country., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© Catholic Medical Association 2019.)

Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) is increasing in adults with severe respiratory failure. Observational data suggest that there are significant challenges to providing adequate nutrition support for patients on vv-ECMO. We aimed to describe firstly the nutrition support practices in a large single-centre providing vv-ECMO to adults and secondly any association with clinical outcome., Methods: We conducted a retrospective review of patients receiving vv-ECMO on the Intensive Care Unit (ICU) of a large London teaching hospital. Adult patients admitted to the ICU with severe respiratory failure between December 2010 and December 2015 were included. Daily energy and protein delivery were compared with estimated targets and reasons for feeding interruptions were collected from electronic medical records. Adequate feeding was defined as 80-110% of estimated targets., Results: We analysed 203 eligible patients. Median duration of ICU stay was 21.0 (IQR, 15.0-33.0) days and vv-ECMO 10.0 (IQR, 7.0-16.0) days. Although median energy (89.8% (IQR, 80.5-96.0%)) and protein (84.7% (IQR, 74.0-96.7%)) delivery was adequate, underfeeding of either energy or protein occurred on nearly one third (28.3%) of nutrition support days. A higher admission severity of illness score was associated with inadequate protein delivery (p = 0.040). Patients with more severe organ dysfunction on the first day of vv-ECMO received inadequate energy (p = 0.026). The most common reasons for interrupted feeding were medical procedures (39.1%) followed by poor gastric motility (22.8%)., Conclusion: Adequate energy and protein delivery during vv-ECMO is possible but underfeeding is still common, especially in those who are more severely ill or who have more severe organ dysfunction. Patients with inadequate energy or protein delivery did not differ in ICU and 6-month survival. Prospective studies investigating optimal feeding in this patient cohort are required., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

We investigated a subtype of Telogen Effluvium associated with Dysesthesia, (TED) which was defined as the presence of Telogen Effluvium with severe itch, pain, soreness, burning, or formication in the absence of any inflammatory scalp disorder or medication associated with Telogen Effluvium or Dysesthesia. These are patients who present with a “burning” scalp or other dysesthesia associated with increased telogen hair shedding. Telogen Effluvium is not typically associated with any scalp symptoms.3 Other scalp dysesthesia studies have mentioned occasional patients in their study that were also diagnosed with Telogen Effluvium,1,2 but the clinical association of Scalp Dysesthesia and Telogen Effluvium has never been made as a distinct entity.

Conventional methods for the determination of major nutrients and trace elements in grass rely on acid digestion followed by analysis using inductively coupled plasma optical emission spectrometry (ICP-OES), which can be both time consuming and costly. Energy dispersive X-ray fluorescence (EDXRF) spectrometry offers a rapid alternative that can determine multiple elements in a single scan. Copper, Mn, Zn, and S in grass samples were determined using EDXRF with a number of different calibration approaches using both empirical standards and the theoretical relationships between concentrations and intensities. Using an existing archive of 467 grass samples of known concentrations, a suite of 30 samples was selected as empirical grass standards to build a calibration set between sample concentrations and EDXRF intensities. The theoretical or standardless approach used the fundamental parameters method to determine element concentrations. To validate the two calibration methods, 59 samples were randomly selected from the same archive and database and analyzed by EDXRF. The measurements of Cu, Mn, Zn, and S were compared with the ICP-OES values using agreement statistics. An excellent correlation was observed between the concentrations determined by EDXRF and ICP-OES ( R > 0.90) regardless of the calibration approach. However, agreement and closeness to the true value varied and were assessed using agreement statistics. Across all elements, the empirically calibrated samples were in excellent agreement with the values determined by ICP-OES. The theoretical calibrations provided excellent agreement for Mn and Zn, but a degree of fixed and proportional bias was observed in the Cu and S values. Fixed bias was corrected by subtracting the computed bias from the EDXRF concentrations and improved the overall agreement. Similarly, proportional bias was corrected using the linear regression model to predict the corrected EDXRF values. This improved the overall agreement with the ICP-OES values for both Cu and S using corrected fundamental parameters calibrations. This study provides a practical basis for the use of EDXRF to determine Cu, Mn, Zn, and S in grass samples to monitor forage quality in grazed systems without the need for sample digestion. The observed fixed and proportional bias in the theoretical calibrations can be corrected provided that a good correlation exists between EDXRF and conventional methods.

The adoption of nutrient management practices can lead to win-win outcomes in terms of both improving productivity and reducing the environmental impact of farming. However, adoption of key practices remains below expectations globally. Few studies specifically focus on the adoption of nutrient management practices and the majority overlook psychological factors in their analysis. This study examines the factors which influence Irish farmers' intention to apply fertiliser on the basis of soil test results. An expanded version of the theory of planned behaviour is used as a framework for analysis. The influence of policy is also accounted for by this study which requires certain farmers in Ireland to adopt soil testing on a mandatory basis. The results for the national sample (n = 1009) show that attitudes, subjective norms (social pressure), perceived behavioural control (ease/difficulty) and perceived resources are significant and positively associated with farmers' intentions. In terms of the voluntary sample (n = 587), only attitude, perceived behavioural control and perceived resources are significantly and positively associated with farmers' intentions. Whereas, for the mandatory sample (n = 422), subjective norms, perceived behavioural control and perceived resources are significantly and correlated in a positive direction with intentions. A number of farm and farmer characteristics are also significantly associated with intentions. Policy recommendations are made based on these results., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Most water and nutrients essential for plant growth travel across a thin zone of soil at the interface between roots and soil, termed the rhizosphere. Chemicals exuded by plant roots can alter the fluid properties, such as viscosity, of the water phase, potentially with impacts on plant productivity and stress tolerance. In this paper, we study the effects of plant exudates on the macroscale properties of water movement in soil. Our starting point is a microscale description of two fluid flow and exudate diffusion in a periodic geometry composed from a regular repetition of a unit cell. Using multiscale homogenization theory, we derive a coupled set of equations that describe the movement of air and water, and the diffusion of plant exudates on the macroscale. These equations are parametrized by a set of cell problems that capture the flow behaviour. The mathematical steps are validated by comparing the resulting homogenized equations to the original pore scale equations, and we show that the difference between the two models is ≲7% for eight cells. The resulting equations provide a computationally efficient method to study plant-soil interactions. This will increase our ability to predict how contrasting root exudation patterns may influence crop uptake of water and nutrients., Competing Interests: The authors have no conflict of interest to declare.

We show how a combination of X-ray computed tomography (X-CT) and image-based modelling can be used to calculate the effect of moisture content and compaction on the macroscopic structural properties of soil. Our method is based on the equations derived in Daly & Roose (2018 Proc. R. Soc. A 474 , 20170141. (doi:10.1098/rspa.2017.0141)), which we have extended so they can be directly applied to the segmented images obtained from X-CT. We assume that the soils are composed of air-filled pore space, solid mineral grains and a mixed phase composed of both clay particles and water. We considered three different initial soil treatments, composed of two different compaction levels and two different moisture contents. We found that the effective properties of the soils were unaffected by compaction over the range tested in this paper. However, changing the moisture content significantly altered the hydraulic and mechanical properties of the soils. A key strength of this method is that it enables the optimization or even design of soils composed from different constituents, with specific mechanical and hydraulic properties.

Background: Heart failure (HF) is a chronic condition causing nearly 1 million hospital admissions annually in the United States with 25% of patients rehospitalized within 30 days., Introduction: The purpose of this study was to investigate whether telemanagement of HF patients throughout the post-acute continuum of care would reduce rehospitalization rates and improve patient self-care knowledge and satisfaction., Materials and Methods: HF patients discharged to a skilled nursing facility (SNF) received telemanagement by HF clinicians with opportunity for continuation at home with assistance of home healthcare (HHC) nurses. Wireless sensors worn at SNF and home captured continuous health information visible to HF clinicians on secure cloud database. Point-of-care devices were available at SNF. Patients had scheduled and as-needed video visits with audio and auscultation capacity with HF clinician. HF education was provided by SNF and HHC nursing. Patients were compared with historical control group receiving standard care at same SNF., Results: Patients receiving telemanagement had 29% lower rehospitalization rates (17% vs. 24%), despite higher predicted rehospitalization risk. Median age was 81. Seven of eight patients who were rehospitalized in the telemanagement group had advanced HF symptoms (New York Heart Association Class IV). Five patients in telemanagement group were receiving continuous inotrope infusions. Patients reported good satisfaction and self-care knowledge., Discussion: Reduction of rehospitalization rates was clinically significant in population of advanced age and HF symptoms. Technology enhanced communication content and timeliness across the post-acute care continuum., Conclusion: Post-acute telemanagement may reduce rehospitalization rates even in high-risk, older HF populations.

Introduction: The role of extracorporeal support for patients with septic shock remains unclear., Methods: We conducted a retrospective analysis of our single-centre experience with veno-arterio-venous extracorporeal membrane oxygenation (VAV ECMO) in adult patients with severe respiratory failure and septic cardiomyopathy. Clinical data was extracted from electronic medical records including a dedicated ECMO referral and follow-up database., Results: Twelve patients were commenced on VAV ECMO for septic cardiomyopathy for a median of four days (IQR 3.0 to 5.3) between 01/2014 and 12/2017. Five patients (41.7%) had a cardiac arrest prior to initiation of ECMO support. At baseline, median left ventricular ejection fraction was 16.25% (IQR 13.13 to 17.5) and median PaO 2 /FiO 2 ratio was 9 kPa (IQR 6.5 to 12.0) [67.50 mmHg (IQR 48.75 to 90.00)]. The survival rate to hospital discharge for VAV ECMO was 75% in this cohort. None of the surviving patients died within the follow-up period (median six month)., Conclusion: VAV ECMO is a feasible rescue strategy for a small proportion of patients with combined respiratory and cardiac failure secondary to septic shock with septic cardiomyopathy. We provide a detailed report of our experience with this technique. Further research is required comparing the different extracorporeal strategies directly to conventional resuscitation and against each other.

We use a spatially explicit biogeochemical end-to-end ecosystem model, Atlantis, to simulate impacts from the Deepwater Horizon oil spill and subsequent recovery of fish guilds. Dose-response relationships with expected oil concentrations were utilized to estimate the impact on fish growth and mortality rates. We also examine the effects of fisheries closures and impacts on recruitment. We validate predictions of the model by comparing population trends and age structure before and after the oil spill with fisheries independent data. The model suggests that recruitment effects and fishery closures had little influence on biomass dynamics. However, at the assumed level of oil concentrations and toxicity, impacts on fish mortality and growth rates were large and commensurate with observations. Sensitivity analysis suggests the biomass of large reef fish decreased by 25% to 50% in areas most affected by the spill, and biomass of large demersal fish decreased even more, by 40% to 70%. Impacts on reef and demersal forage caused starvation mortality in predators and increased reliance on pelagic forage. Impacts on the food web translated effects of the spill far away from the oiled area. Effects on age structure suggest possible delayed impacts on fishery yields. Recovery of high-turnover populations generally is predicted to occur within 10 years, but some slower-growing populations may take 30+ years to fully recover.

In this paper, we use homogenization to derive a set of macro-scale poro-elastic equations for soils composed of rigid solid particles, air-filled pore space and a poro-elastic mixed phase. We consider the derivation in the limit of large deformation and show that by solving representative problems on the micro-scale we can parametrize the macro-scale equations. To validate the homogenization procedure, we compare the predictions of the homogenized equations with those of the full equations for a range of different geometries and material properties. We show that the results differ by [Formula: see text] for all cases considered. The success of the homogenization scheme means that it can be used to determine the macro-scale poro-elastic properties of soils from the underlying structure. Hence, it will prove a valuable tool in both characterization and optimization., Competing Interests: The authors have no conflict of interest to declare.

The parameters in Richards' equation are usually calculated from experimentally measured values of the soil-water characteristic curve and saturated hydraulic conductivity. The complex pore structures that often occur in porous media complicate such parametrization due to hysteresis between wetting and drying and the effects of tortuosity. Rather than estimate the parameters in Richards' equation from these indirect measurements, image-based modelling is used to investigate the relationship between the pore structure and the parameters. A three-dimensional, X-ray computed tomography image stack of a soil sample with voxel resolution of 6 μm has been used to create a computational mesh. The Cahn-Hilliard-Stokes equations for two-fluid flow, in this case water and air, were applied to this mesh and solved using the finite-element method in COMSOL Multiphysics. The upscaled parameters in Richards' equation are then obtained via homogenization. The effect on the soil-water retention curve due to three different contact angles, 0°, 20° and 60°, was also investigated. The results show that the pore structure affects the properties of the flow on the large scale, and different contact angles can change the parameters for Richards' equation., Competing Interests: We declare we have no competing interests.

Objectives: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage., Design: A single-center, retrospective, observational cohort study., Setting: Tertiary referral severe respiratory failure center, university teaching hospital., Patients: Patients admitted between December 2011 and February 2016., Intervention: None., Measurements and Main Results: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (g/L) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%., Conclusions: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.

Mainstream sentencing courts do little to change the behavior of partner violence offenders, let alone members of more socially marginal groups. Indigenous offenders face a court system that has little relevance to the complexity of their relations and lived experiences. Assisted by respected Elders and Community Representatives, Australian Indigenous sentencing courts seek to create a more meaningful sentencing process that has a deeper impact on Indigenous offenders' attitudes and, ultimately, their behavior. Drawing from interviews with 30 Indigenous offenders, we explore the ways in which the courts can motivate Indigenous partner violence offenders on pathways to desistence.

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na + /glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.

Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000-40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic.

Agriculture has been implicated in the loss of pristine conditions and ecology at river sites classified as at 'high ecological status' across Europe. Although the exact causes remain unclear, diffuse phosphorus (P) transfer warrants consideration because of its wider importance for the ecological quality of rivers. This study assessed the risk of P loss at field scale from farms under contrasting soil conditions within three case-study catchments upstream of near-pristine river sites. Data from 39 farms showed P surpluses were common on extensive farm enterprises despite a lower P requirement and level of intensity. At field scale, data from 520 fields showed that Histic topsoils with elevated organic matter contents had low P reserves due to poor sorption capacities, and received applications of P in excess of recommended rates. On this soil type 67% of fields recorded a field P surplus of between 1 and 31kgha -1 , accounting for 46% of fields surveyed across 10 farms in a pressured high status catchment. A P risk assessment combined nutrient management, soil biogeochemical and hydrological data at field scale, across 3 catchments and the relative risks of P transfer were highest when fertilizer quantities that exceeded current recommendations on soils with a high risk of mobilization and high risk of transport as indicated by topographic wetness index values. This situation occurred on 21% of fields surveyed in the least intensively managed catchment with no on-farm nutrient management planning and soil testing. In contrast, the two intensively managed catchments presented a risk of P transfer in only 3% and 1% of fields surveyed across 29 farms. Future agri-environmental measures should be administered at field scale, not farm scale, and based on soil analysis that is inclusive of OM values on a field-by-field basis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Congenital cytomegalovirus is the most frequent, yet under-recognised, infectious cause of newborn malformation in developed countries. Despite its clinical and public health importance, questions remain regarding the best diagnostic methods for identifying maternal and neonatal infection, and regarding optimal prevention and therapeutic strategies for infected mothers and neonates. The absence of guidelines impairs global efforts to decrease the effect of congenital cytomegalovirus. Data in the literature suggest that congenital cytomegalovirus infection remains a research priority, but data are yet to be translated into clinical practice. An informal International Congenital Cytomegalovirus Recommendations Group was convened in 2015 to address these questions and to provide recommendations for prevention, diagnosis, and treatment. On the basis of consensus discussions and a review of the literature, we do not support universal screening of mothers and the routine use of cytomegalovirus immunoglobulin for prophylaxis or treatment of infected mothers. However, treatment guidelines for infected neonates were recommended. Consideration must be given to universal neonatal screening for cytomegalovirus to facilitate early detection and intervention for sensorineural hearing loss and developmental delay, where appropriate. The group agreed that education and prevention strategies for mothers were beneficial, and that recommendations will need continual updating as further data become available., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mucosa-associated microbial populations of the gastrointestinal tract are in intimate contact with the outer mucus layer. This proximity offers these populations a higher potential, than lumenal microbiota, in exerting effects on the host. Functional characteristics of the microbiota and influences of host-physiology shape the composition and activity of the mucosa-associated bacterial community. We have shown previously that inclusion of an artificial sweetener, SUCRAM, included in the diet of weaning piglets modulates the composition of lumenal-residing gut microbiota and reduces weaning-related gastrointestinal disorders. In this study, using Illumina sequencing we characterised the mucosa-associated microbiota along the length of the intestine of piglets, and determined the effect of SUCRAM supplementation on mucosa-associated populations. There were clear distinctions in the composition of mucosa-associated microbiota, between small and large intestine, concordant with differences in regional oxygen distribution and nutrient provision by the host. There were significant differences in the composition of mucosa-associated compared with lumenal microbiota in pig caecum. Dietary supplementation with SUCRAM affected mucosa-associated bacterial community structure along the length of the intestinal tract. Most notably, there was a substantial reduction in predominant Campylobacter populations proposing that SUCRAM supplementation of swine diet has potential for reducing meat contamination and promoting food safety., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The clinical benefit of nab-paclitaxel monotherapy for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) that progressed on other taxanes (cremophor-based paclitaxel or docetaxel) is unknown. A retrospective analysis of patients treated at a single institution with nab-paclitaxel for taxane-resistant RM-HNSCC. The exploratory hypothesis was that nab-paclitaxel would result in clinical benefit (tumor response) in patients with taxane-resistant RM-HNSCC. Twelve patients who were treated with nab-paclitaxel monotherapy for taxane-resistant RM-HNSCC and met all eligibility criteria were identified. The majority of patients (n = 9; 75%) received three or more lines of therapy for RM-HNSCC. All patients had platin-resistant, and ten patients (83%) had cetuximab-resistant disease. Patients had RM-HNSCC that progressed on cremophor-based paclitaxel (8), docetaxel (1), or both (3). With prior taxane, the best tumor response was partial (PR) in 4 patients (33%), stable (SD) in 3 (25%), and progression in 5 (42%). The median time-to-progression (TTP) with prior taxane was 1.7 (range 0.7-9.0) months. The median interval from last dose of taxane to first dose of nab-paclitaxel was 3 (0.7-31.3) months. With nab-paclitaxel, tumor response occurred in two patients (17%; PR in both) and disease control (PR and SD) occurred in five (42%). Median TTP with nab-paclitaxel was 2.1 months (range 0.6-6.2), and median overall survival was 4.9 months (range 1.9-13.5). nab-Paclitaxel provided clinical benefit in some patients with taxane-resistant RM-HNSCC. The median TTP with nab-paclitaxel and with prior taxane were similar. This exploratory observation warrants further investigation in prospective studies.