Search

Background: The CEA/PCI ratio, which evaluates tumour marker and burden, has been demonstrated as a prognosticator for patients with colorectal cancer with peritoneal carcinomatosis. The aim of this study was to compare the CEA/PCI ratio with the Modified Colorectal Peritoneal Score (mCOREP) for overall survival (OS) and recurrence free survival (RFS). There is no literature currently comparing both markers for RFS. Methods: Data was collected retrospectively for patients undergoing CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) at the Peritonectomy Unit at St. George Hospital, NSW from January 2015 to December 2021. Results: From 187 patients, an increase in CEA/PCI ratio was associated with reduced OS (p 4 illustrated reduced RFS in patients with lower PCIs.

Pseudomyxoma peritonei is a rare peritoneal malignancy characterized by the progressive accumulation of mucinous material and tumour within the abdomen and pelvis. Percutaneous drainage of mucin may be a non-surgical option for relief of symptoms; however, it remains difficult due to the high viscosity of mucin, with numerous case reports reporting difficulty removing material through medium-bore catheters alone. BromAc is a therapy currently undergoing development which dissolves mucinous tumour masses and allows for extraction. This report describes the case of a patient who has had multiple treatments with BromAc over 4 years.

Objective To introduce the Community Resiliency Model (CRM) as mental well-being support for healthcare workers working through the height of the COVID-19 pandemic.Design Randomised controlled trial with a no treatment control group.Setting Two large urban health systems in the Southern United States between October 2020 and June 2021.Participants Eligible participants were currently employed as healthcare workers within the participating healthcare systems. 275 employees registered and consented electronically in response to email invitations. 253 participants completed the baseline survey necessary to be randomised and included in analyses.Intervention Participants were assigned 1:1 to the control or intervention group at the time of registration. Intervention participants were then invited to 1-hour virtual CRM class teaching skills to increase somatic awareness in the context of self and other care.Main outcome measures Self-reported data were collected rating somatic awareness, well-being, symptoms of stress, work engagement and interprofessional teamwork.Results Baseline data on the total sample of 275 (53% nurses) revealed higher symptoms of stress and lower well-being than the general population. The intervention participants who attended a CRM class (56) provided follow-up survey data at 1 week (44) and 3 months (36). Significant improvement for the intervention group at 3 months was reported for the well-being measures (WHO-5, p

Low resistance n+GaN contact materials were experimentally studied for GaN HEMT applications by selective area epitaxy regrowth on a patterned SiC substrate. Epitaxy was performed by metal organic chemical vapor deposition using 100% H2 or 100% N2 as the carrier gas. Thin film characterization demonstrated that n+GaN grown in N2 carrier gas has a superior morphology with improved crystalline quality to that grown in H2 carrier gas. The results also indicated that the surface morphology of n+GaN grown in N2 carrier gas is less sensitive to mask pattern density and micro-loading effects with Si doping concentrations up to 1 × 1020/cm3. Secondary ion mass spectrometry analysis shows that C and O impurity levels in n+GaN are one order of magnitude lower with N2 carrier gas than with H2. The electrical measurement of transmission line model structures shows an n+GaN sheet resistance of 15 Ω/sq and an Ohmic metal to n+GaN contact resistance of 0.02 Ω-mm for structures grown in N2 carrier gas. These values represent 7.1× and 2.5× improvements compared to H2 carrier gas.

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

COVID-19 is an established threat whose clinical features and epidemiology continues to evolve. In an effort to contain the disease, the National Health Service has adopted a digital first approach in UK general practice resulting in a significant shift away from face-to-face consultations. Consequently, more consultations are being completed without obtaining objective recording of vital signs and face-to-face examination. Some regions have formed hot hubs to facilitate the review of suspected COVID-19 cases and keep their practice site ‘clean’ including the use of doorstep observations in avoiding the risk of face-to-face examination. To support the safe, effective and efficient remote assessment of suspected and confirmed patients with COVID-19, we established a doorstep assessment service to compliment telephone and video consultations. This allows physiological parameters such as temperature, pulse, blood pressure and oxygen saturation to be obtained to guide further triage. Quality improvement methods were used to integrate and optimise the doorstep assessment and measure the improvements made. The introduction of a doorstep assessment service increased the proportion of assessments for patients with suspected COVID-19 in routine care over weeks. At the same time we were able to dramatically reduce face-to-face assessment over a 6-week period by optimising through a range of measures including the introduction of a digital stethoscope. The majority of patients were managed by their own general practitioner following assessment supporting continuity of care. There were no adverse events during the period of observation; no staff absences related to COVID-19. Quality improvement methods have facilitated the successful integration of doorstep assessments into clinical care.

Background Radiotherapy (RT) has been shown to stimulate an antitumor immune response in irradiated tumors as well as unirradiated distant sites (abscopal effect). Previous studies have demonstrated a role for the tumor-draining lymph node (LN) in mediating an anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) stimulated antitumor immune response. Here, we investigated whether the LN is also important in mediating a RT alone stimulated abscopal response.Methods We used a subcutaneous modified B16F10 flank tumor model injected bilaterally. Our B16F10 cell line has an inserted viral glycoprotein which facilitated identification of tumor-specific T-cells. RT was directed at one flank tumor alone or one flank tumor and the tumor-draining LN. We evaluated response by tumor growth measurements and flow cytometry of both tumor-infiltrating and LN T-cells.Results We show that local tumor irradiation improves distant tumor control (abscopal effect). Depletion of CD8+ T-cells significantly reduced this abscopal response. We have previously shown, in a chronic lymphocytic choriomeningitis virus (LCMV) infection, that the T-cell proliferative burst following blockade of PD-1/L1 is provided by a ‘stem-like’ CD8+ T-cell subset which then differentiate into terminally differentiated effectors. These terminally differentiated effectors have the potential to kill virally infected or tumor cells following PD-1/L1 blockade. In the chronic LCMV infection, stem-like CD8+ T-cells were found exclusively in secondary lymphoid organs. Similarly, here we found these cells at high frequencies in the tumor-draining LN, but at low frequencies within the tumor. The effect of RT on this T-cell subset in unknown. Interestingly, tumor irradiation stimulated total CD8+ and stem-like CD8+ T-cell proliferation in the LN. When the LN and the tumor were then targeted with RT, the abscopal effect was reduced, and we found a concomitant reduction in the number of total tumor-specific CD8+ T-cells and stem-like CD8+ T-cells in both the irradiated and unirradiated tumor.Conclusions These correlative results suggest the tumor-draining LN may be an important mediator of the abscopal effect by serving as a stem-like CD8+ T-cell reservoir, a site for stem-like T-cell expansion, and a site from which they can populate the tumor.

Abstract Background Ipilimumab is an FDA-approved anti-CTLA-4 monoclonal antibody used in treatment of metastatic melanoma. We present an unusual neurological complication of Ipilimumab therapy and the diagnostic dilemma it caused. Case presentation A 42 year old male with Stage IV metastatic melanoma developed lower extremity weakness and sensory neuropathy following three doses of Ipilimumab. MRI of the lumbar spine was initially interpreted as diffuse leptomeningeal disease, and patient began Dexamethasone and radiation with improvement in symptoms. However, subsequent completion imaging revealed smooth nerve root involvement with sparing of the spinal cord, findings more compatible with inflammatory demyelinating polyneuropathy. The absence of malignant cells in the cerebrospinal fluid (CSF) and nerve conduction study (NCS) showing lumbar polyradiculoneuropathy with axonal involvement and demyelinating features supported the diagnosis of inflammatory demyelinating polyneuropathy. Later in the course of his disease, the patient developed frank leptomeningeal melanoma. Conclusion Ipilimumab immune-related toxicity presented as inflammatory demyelinating polyneuropathy, which was difficult to distinguish from leptomeningeal disease, a common complication of melanoma.

Tropical land-use change for agricultural expansion is the primary driver of global biodiversity decline. Efforts to stem this decline often focus on protecting pristine habitats or returning farmland to forest, yet such approaches fail to protect vulnerable taxa reliant on habitats within low-intensity farmland. We assess the economic viability of carbon-based payments for ecosystem services (PES) to protect farmland trees and fallowing in Ghana, which provide vital wintering sites for imperiled Afro-palearctic migrant birds and enhance landscape-level carbon storage. We estimate the carbon breakeven prices (BEPs) associated with alternative agricultural management scenarios that protect existing farmland trees. BEPs associated with tree protection on existing farmland were very low, ranging from US$2.49 to US$6.45 t ^−1 CO _2 . Extending and reintroducing fallow periods also carried competitive BEPs, US$4.67—US$15.45 t ^−1 CO _2 , when combined with the protection of 50 trees per hectare. Accounting for leakage and economic uncertainty increased BEPs considerably, but scenarios protecting farmland trees and extending fallow periods remained below EU Emissions Trading Scheme prices. Protecting low-intensity farmland habitats and associated biodiversity is cost-effective under carbon-based PES. Implementation should be combined with efforts to close yield gaps, providing greater local food security and resilience.

Background: Researchers from a variety of disciplines have presented data indicating that polygynous marriage is damaging to child health. This work has been used to support the classification of polygyny as a 'harmful cultural practice' and to advocate for marital reform across sub-Saharan Africa. Objective: We present a critical review of studies of polygyny and child health, highlighting issues of context and variation. We also consider methodological limitations of the existing literature. Methods: We describe key features of African polygyny, variation in its form, and the pathways through which polygyny has been hypothesized to influence child health. We then review the available empirical evidence, focusing on cross-national studies utilizing the Demographic and Health Surveys and relatively small-scale studies based on more specific socioecological settings (e.g., among particular ethnic groups). Conclusions: We conclude that (i) heterogeneity in the impact of polygyny on child health should be anticipated a priori given substantial variety in its form, locally available alternatives, and the wider context of the practice; (ii) available evidence suggests that polygyny is most frequently associated with poor child health, but there are also instances where polygyny appears inconsequential or even beneficial to children; and (iii) methodological shortcomings are rife across the literature, severely undermining our ability to make causal inferences from observed relationships between polygyny and child health. Contribution: Theoretical and empirical considerations imply that a singular health consequence of polygyny does not apply across all ecological and cultural settings. We encourage a more nuanced stance on polygyny in future academic and policy discourse.

We describe how pathway engineering can be used to convert a single intermediate derived from lipid biosynthesis, fatty aldehydes, into a variety of biofuel precursors including alkanes, free fatty acids and wax esters. In cyanobacteria, long-chain acyl-ACPs can be reduced to fatty aldehydes, and then decarbonylated to alkanes. We discovered a cyanobacteria class-3 aldehyde-dehydrogenase, AldE, that was necessary and sufficient to instead oxidize fatty aldehyde precursors into fatty acids. Overexpression of enzymes in this pathway resulted in production of 50 to 100 fold more fatty acids than alkanes, and the fatty acids were secreted from the cell. Co-expression of acyl-ACP reductase, an alcohol-dehydrogenase and a wax-ester-synthase resulted in a third fate for fatty aldehydes: conversion to wax esters, which accumulated as intracellular lipid bodies. Conversion of acyl-ACP to fatty acids using endogenous cyanobacterial enzymes may allow biofuel production without transgenesis.