Stereographic cloud heights from the imagery of two scan-synchronized geostationary satellites

Scan synchronization of the sensors of two SMS-GOES satellites yields imagery from which cloud heights can be derived stereographically with a theoretical two-sigma random uncertainty of + or - 0.25 km for pairs of satellites separated by 60 degrees of longitude. Systematic height errors due to cloud motion can be kept below 100 m for all clouds with east-west components of speed below hurricane speed, provided the scan synchronization is within 40 seconds at the mid-point latitude, and the spin axis of each satellite is parallel to that of the earth

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 antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) 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 restimulation 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. Antitumor 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

“Just keep pushing”: parents’ experiences of accessing child and adolescent mental health services for child anxiety problems

Background:Anxiety disorders are among the most common psychopathologies in childhood, however a high proportion of children with anxiety disorders do not access effective treatments.The aim of the present qualitative study was to understand families’ experiences of seeking help and accessing specialist treatment for difficulties with childhood anxiety.Methods:Parents of 16 children (aged 7-12 years) referred to a child mental health service for difficulties with anxiety, were interviewed about their experiences of seeking and accessing treatment within CAMHS. All interviews were transcribed verbatim and thematically analysed for similarities and differences in families’ experiences. Results:Factors that helped and/or hindered families accessing treatment related to: i) parental recognition, ii) contact with professionals, iii) reaching CAMHS, iv) parental effort, and v) parental knowledge and concerns. High demands on services and parents’ uncertainty surrounding the help-seeking process presented key hurdles for families. The critical role of parental persistence and support from GPs and school staff was evident across interviews.Conclusions:Findings highlighted the need for information and guidance on identifying child anxiety difficulties and professional, peer and self-help support; and ensuring sufficient provision is available to allow families prompt access to support

Expedition 390 Preliminary Report. South Atlantic Transect 1

The South Atlantic Transect (SAT) is a multidisciplinary scientific ocean drilling project that comprises four International Ocean Discovery Program (IODP) expeditions: engineering Expeditions 390C and 395E as well as Expeditions 390 and 393. Altogether, the expeditions aim to recover complete sedimentary sections and the upper 100–350 m of the underlying oceanic crust along a slow/intermediate spreading rate Mid-Atlantic Ridge crustal flow line at ~31°S. The sediments along this transect were originally spot cored more than 50 y ago during Deep Sea Drilling Project Leg 3 (December 1968–January 1969) to help verify the theories of seafloor spreading and plate tectonics. Given dramatic advances in drilling technology and analytical capabilities since Leg 3, many high-priority scientific objectives can be addressed by revisiting the transect. The SAT expeditions target six primary sites on 7, 15, 31, 49, and 61 Ma ocean crust, which fill critical gaps in our sampling of intact in situ ocean crust with regards to crustal age, spreading rate, and sediment thickness. Drilling these sites is required to investigate the history of the low-temperature hydrothermal interactions between the aging ocean crust and the evolving South Atlantic Ocean and quantify past hydrothermal contributions to global biogeochemical cycles. Samples from the transect of the previously unexplored sediment- and basalt-hosted deep biosphere beneath the South Atlantic Gyre are essential to refining global biomass estimates and examining microbial ecosystems’ responses to variable conditions in a low-energy gyre and aging ocean crust. The transect is located near World Ocean Circulation Experiment Line A10, providing access to records of carbonate chemistry and deepwater mass properties across the western South Atlantic through key Cenozoic intervals of elevated atmospheric CO2 and rapid climate change. Reconstruction of the history of the deep western boundary current and deepwater formation in the Atlantic basins will yield crucial data to test hypotheses regarding the role of evolving thermohaline circulation patterns in climate change and the effects of tectonic gateways and climate on ocean acidification. Engineering Expeditions 390C and 395E cored a single hole through the sediment/basement interface with the advanced piston corer/extended core barrel system at five of the six primary proposed SAT sites and installed a reentry system with casing either into basement or within 10 m of basement at each of those five sites. Expedition 390 (7 April–7 June 2022) conducted operations at three of the SAT sites, recovering 700 m of core (77% recovery) over 30.3 days of on-site operations. Sediment coring, basement drilling, and logging were conducted at two sites on 61 Ma crust, and sediment coring was completed at the 7 Ma crust site. At Site U1557 on 61 Ma crust, the drill bit was deposited on the seafloor prior to downhole logging, leaving Hole U1557D available for future deepening and to establish a legacy borehole for basement hydrothermal and microbiological experiments. Expedition 390 scientists additionally described, and analyzed data from, 792 m of core collected during Expeditions 390C and 395E. Expedition 393 plans to operate at four sites, conducting basement drilling and downhole logging at the 7 Ma site, in addition to sediment coring, basement drilling, and logging at the sites intermediate in age

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

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

What do parents perceive are the barriers and facilitators to accessing psychological treatment for mental health problems in children and adolescents? A systematic review of qualitative and quantitative studies

A minority of children and adolescents with mental health problems access treatment. The reasons for poor rates of treatment access are not well understood. As parents are a key gatekeeper to treatment access, it is important to establish parents’ views of barriers/facilitators to accessing treatment. The aims of this study are to synthesise findings from qualitative and quantitative studies that report parents’ perceptions of barriers/facilitators to accessing treatment for mental health problems in children/adolescents. A systematic review and narrative synthesis were conducted. Forty-four studies were included in the review and were assessed in detail. Parental perceived barriers/facilitators relating to (1) systemic/structural issues; (2) views and attitudes towards services and treatment; (3) knowledge and understanding of mental health problems and the help-seeking process; and (4) family circumstances were identified. Findings highlight avenues for improving access to child mental health services, including increased provision that is free to service users and flexible to their needs, with opportunities to develop trusting, supportive relationships with professionals. Furthermore, interventions are required to improve parents’ identification of mental health problems, reduce stigma for parents, and increase awareness of how to access services

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

Fault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging-wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP-2). We present observational evidence for extensive fracturing and high hanging-wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP-2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging-wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off-fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation