A note on the fluxes of abiogenic methane and hydrogen from mid-ocean ridges

The concentrations of methane and hydrogen in hydrothermal vent fluids issuing from mid-ocean ridges tend to fall into two groups, one with high concentrations of these gases in ultramafic-hosted vent fields and a second group with relatively lower concentrations in basalt-hosted vent fluids. Ultramafic-hosted systems, however, appear to be restricted to slow-spreading ridges and constitute only a fraction of the hydrothermal systems found there. In this note, the hydrothermal fluxes of methane and hydrogen have been calculated by estimating the percentages of the total subsurface hydrothermal circulation that circulate through each type of host rock. Even though the percentage of the total subsurface flow that is affected by serpentinization appears to be rather small (8%), it still appears that this process produces about 70% of the total mid-ocean flux of these gases. The total production of methane and hydrogen is calculated to be about 20 x 10(9) mol yr(-1) and 190 x 10(9) mol yr(-1), respectively. The hydrogen flux is comparable to that most recently calculated on the basis of the rate of hydration of mantle rock in newly formed crust and the stoichiometry of the serpentinization reaction. This suggests that, except for the production of methane, a major portion of the hydrogen produced in the subsurface is not consumed before venting

The role of the smartphone in the transition from medical student to foundation trainee: a qualitative interview and focus group study

Background The transition from medical student to junior doctor is one of the most challenging in medicine, affecting both doctor and patient health. Opportunities to support this transition have arisen from advances in mobile technology and increased smartphone ownership. Methods This qualitative study consisted of six in-depth interviews and two focus groups with Foundation Year 1 Trainees (intern doctors) and final year medical students within the same NHS Trust. A convenience sample of 14 participants was recruited using chain sampling. Interviews and focus groups were recorded, transcribed verbatim, analysed in accordance with thematic analysis and presented below in keeping with the standards for reporting qualitative research. Results Participants represented both high and low intensity users. They used their smartphones to support their prescribing practices, especially antimicrobials through the MicroGuide™ app. Instant messaging, via WhatsApp, contributed to the existing bleep system, allowing coordination of both work and learning opportunities across place and time. Clinical photographs were recognised as being against regulations but there had still been occasions of use despite this. Concerns about public and colleague perceptions were important to both students and doctors, with participants describing various tactics employed to successfully integrate phone use into their practices. Conclusion This study suggests that both final year medical students and foundation trainees use smartphones in everyday practice. Medical schools and healthcare institutions should seek to integrate such use into core curricula/training to enable safe and effective use and further ease the transition to foundation training. We recommend juniors are reminded of the potential risks to patient confidentiality associated with smartphone use

Incursion of meteoric waters into the ductile regime in an active orogen

Rapid tectonic uplift on the Alpine Fault, New Zealand, elevates topography, regional geothermal gradients, and the depth to the brittle ductile transition, and drives fluid flow that influences deformation and mineralisation within the orogen. Oxygen and hydrogen stable isotopes, fluid inclusion and Fourier Transform Infrared (FT-IR) analyses of quartz from veins which formed at a wide range of depths, temperatures and deformation regimes identify fluid sources and the depth of penetration of meteoric waters. Most veins formed under brittle conditions and with isotope signatures (δ18OH2O = −9.0 to +8.7‰VSMOW and ‰ ) indicative of progressively rock-equilibrated meteoric waters. Two generations of quartz veins that post-date mylonitic foliation but endured further ductile deformation, and hence formation below the brittle to ductile transition zone ( depth), preserve included hydrothermal fluids with values between −84 and ‰ , indicating formation from meteoric waters. FT-IR analyses of these veins show no evidence of structural hydrogen release, precluding this as a source of low values. In contrast, the oxygen isotopic signal of these fluids has almost completely equilibrated with host rocks (δ18OH2O = +2.3 to +8.7‰). These data show that meteoric waters dominate the fluid phase in the rocks, and there is no stable isotopic requirement for the presence of metamorphic fluids during the precipitation of ductilely deformed quartz veins. This requires the penetration during orogenesis of meteoric waters into and possibly below the brittle to ductile transition zone

Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months

Purpose: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). Methods: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. Results: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p<0.001), radiotherapy (p<0.05), and reported poorer QoL (p=0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p<0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year. Conclusions: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs

Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion

Background Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell anti-tumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTL) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion. Methods Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic re-stimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout. Results Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Anti-tumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL. Conclusions This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short term augmented effector function against the risk of T cell exhaustion in order to achieve longer term protection. What is already known on this topic • T cell exhaustion in the tumor microenvironment is a major factor limiting the potential success of adoptive cell therapy (ACT) in the treatment of solid tumors. • Deletion of the phosphatase PTPN22 in CD8+ T cells improves their response to tumors, but it is not known whether this influences development of exhaustion. What this study adds • Under conditions which promote exhaustion, CTL lacking PTPN22 exhaust more rapidly than WT cells, despite displaying enhanced effector function in their initial response to antigen. • Ptpn22KO CTL express high levels of the inhibitory receptor TIM-3, but TIM-3 signaling does not directly contribute to Ptpn22KO CTL dysfunction. • Ptpn22KO T cells are more responsive to IL-2 through JAK-STAT signaling, which induces TIM-3 expression via the transcription factor NFIL3. How this study might affect research, practice or policy • Strategies aimed at augmenting T cell effector function for ACT should balance improved responses against an increased risk of T cell exhaustion

Fine-scale variation within urban landscapes affects marking patterns and gastrointestinal parasite diversity in red foxes

Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine‐scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence.Here, we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine‐scale variation in socio‐economic and ecological variables can affect red fox (Vulpes vulpes) marking behavior, gastrointestinal (GI) parasite prevalence, and parasite community diversity.We found that the presence and abundance of red fox fecal markings were nonuniformly distributed across greenspaces and instead were dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness, and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas.Our results suggest that fine‐scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores

Scientific Drilling and Related Research in the Samail Ophiolite, Sultanate of Oman

This workshop report describes plans for scientific drilling in the Samail ophiolite in Oman in the context of past, current, and future research. Long-standing plans to study formation and evolution of the Samail crust and upper mantle, involving igneous and metamorphic processes at an oceanic spreading center, have been augmented by recent interest in ongoing, low temperature processes. These include alteration and weathering, and the associated sub-surface biosphere supported by chemical potential energy due to disequilibrium between mantle peridotite and water near the surface. This interest is motivated in part by the possibility of geological carbon capture and storage via engineered, accelerated mineral carbonation in Oman