Earth-like aqueous debris-flow activity on Mars at high orbital obliquity in the last million years

Liquid water is currently extremely rare on Mars, but was more abundant during periods of high obliquity in the last few millions of years. This is testified by the widespread occurrence of mid-latitude gullies: small catchment-fan systems. However, there are no direct estimates of the amount and frequency of liquid water generation during these periods. Here we determine debris-flow size, frequency and associated water volumes in Istok crater, and show that debris flows occurred at Earth-like frequencies during high-obliquity periods in the last million years on Mars. Results further imply that local accumulations of snow/ice within gullies were much more voluminous than currently predicted; melting must have yielded centimetres of liquid water in catchments; and recent aqueous activity in some mid-latitude craters was much more frequent than previously anticipated

Palliative care coverage across European National Health Systems: proposal of a synthetic indicator

Background: The coverage of palliative care (PC) may be understood as a country’s capacity to offer prevention and relief from serious health-related suffering in relation to an existing need. The aim of this study is to estimate European countries´ coverage capacities. Method: Secondary analysis of three indicators, including the number of specialized services (SSPC), integration capacity scores (ICS) and the PC needs. By means of a K-medians clustering supervised algorithm, three coverage profiles were obtained: (1) Advanced: countries with high ICS and SSPC, and low PC needs; (2) Limited: countries with low ICS and SSPC, and low PC needs; and (3) Low: countries with low ICS and SSPC and high PC needs. Results: On average, the ratio of specialized services per population was 0.79 per 100,000 inhabitants, the average ICS was 19.62 and the average number of deceased patients with SHS per 100,000 inhabitants was 5.69. Twenty countries (41%) reached an advanced coverage profile. Nine countries (18%) demonstrated a limited coverage profile; and 20 countries (41%) fell under a low-coverage capacity. Conclusion: The level of palliative care coverage across Europe shows that 59% of European countries have either limited or very low availability of PC resources as regards their palliative care needs

Development of an atlas of palliative care in the Eastern Mediterranean Region through a stakeholder participative process

Background: The increasing number of people experiencing serious health-related suffering due to severe illness is an urgent issue in the WHO Eastern Mediterranean Region (EMR). Although palliative care can mitigate much of this suffering, its current development and indicators to measure progress remain unknown. Aims: To describe the development of the Atlas of palliative care in the Eastern Mediterranean Region 2021. Methods: Recently, the WHO Regional Office for the Eastern Mediterranean, together with a network of palliative care experts, identified the best indicators and collected data across the Region. These indicators include national palliative care strategies, number of specialized palliative care services per population, inclusion of palliative care in the health benefits package and national health budget, and the use of pain medication. These and other useful information form the Atlas of palliative care in the Eastern Mediterranean Region 2021. Results: The Atlas shows that provision of specialized palliative care services and pain medication in the Region is low. Several of the indicators suitable to the region are new and include the level of public awareness of palliative care, inclusion of palliative care in health insurance plans, availability of centres of excellence for palliative clinical care, and availability of grants to finance palliative care research. Conclusion: Adoption of favourable policies, educational initiatives, and the involvement of stakeholders, represent an opportunity for future development of palliative care in the EMR

Region-specific macroindicators on palliative care development in the Eastern Mediterranean region: a Delphi study

Background: The World Health Organization Office for the Eastern Mediterranean Region (WHO/EMRO), and the recently created palliative care experts network for the Eastern Mediterranean Region (EMR), decided to develop region-specific indicators for monitoring national palliative care development in the Region. Aims: To identify relevant and feasible macro-indicators for palliative care development for the EMR. Methods: Palliative care experts from the EMR were nominated and invited to complete a 2-round Delphi study to rate macro-indicators from previous studies and propose new ones based on the EMR regional characteristics. All indicators were assessed according to regional relevance (R) and feasibility (F). A content validity index (CVI) was calculated. Indicators with CVI ≥ 0.7/1, and scoring ≥ 7/9 for the R and F averages were selected. Results: Twelve of the 22 countries in the Region were represented in the study. In the first round, 11 indicators were selected and 13 new ones proposed. In the second round, 15 indicators matched R, F and CVI criteria. Top-scored indicators were: existence of a current national palliative care strategy (R = 8, F = 8, CVI = 1); ratio of specialized services (for adults and children) in the country per population (R = 8, F = 7, CVI = 1); allocation of funds for palliative care in the national health budget by the Ministry of Health or equivalent government agency (R = 8, F = 6, CVI = 1); education for prequalification of doctors/nurses (R = 8, F = 8, CVI = 0.9); and availability of morphine and other strong opioids (R =8, F = 8, CVI= 0.9). Conclusion: A baseline set of 15 region-specific indicators for measuring the development of palliative care were validated by experts in the EMR

Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention

BackgroundTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic opportunities. Recently, splicing factors have gained attention as potential targets for cancer treatment. Here we systematically evaluated the role of RNA splicing factors in TNBC cell proliferation.MethodsIn this study, we performed an RNAi screen targeting 244 individual splicing factors to systematically evaluate their role in TNBC cell proliferation. For top candidates, mechanistic insight was gained using amongst others western blot, PCR, FACS, molecular imaging and cloning. Pulldown followed by mass spectrometry were used to determine protein-protein interactions and patient-derived RNA sequencing data was used relate splicing factor expression levels to proliferation markers.ResultsWe identified nine splicing factors, including SNRPD2, SNRPD3 and NHP2L1, of which depletion inhibited proliferation in two TNBC cell lines by deregulation of sister chromatid cohesion (SCC) via increased sororin intron 1 retention and down-regulation of SMC1, MAU2 and ESPL1. Protein-protein interaction analysis of SNRPD2, SNRPD3 and NHP2L1 identified that seven out of the nine identified splicing factors belong to the same spliceosome complex including novel component SUN2 that was also critical for efficient sororin splicing. Finally, sororin transcript levels are highly correlated to various proliferation markers in BC patients.ConclusionWe systematically determined splicing factors that control proliferation of breast cancer cells through a mechanism that involves effective sororin splicing and thereby appropriate sister chromatid cohesion. Moreover, we identified SUN2 as an important new spliceosome complex interacting protein that is critical in this process. We anticipate that deregulating sororin levels through targeting of the relevant splicing factors might be a potential strategy to treat TNBC.Cancer Signaling networks and Molecular Therapeutic

Palliative care in the Eastern Mediterranean: comparative analysis using specific indicators

Background Monitoring the development of palliative care (PC) illustrates the capacity of health systems to respond to the needs of people experiencing serious health-related suffering. Aim To analyse comparatively the situation of PC in the countries of the Easter Mediterranean region using context-specific indicators. Method An online questionnaire with 15 context-specific PC indicators investigating service provision, use of medicines, policy, education, and vitality was designed. Authors Institution 1 nominated in-country experts to complete the survey. Data were analysed using a comparative description of indicators per domain and a multivariate analysis. Results In-country experts were identified in 17/22 countries. 12/17 contributed to the survey. In total, 117 specialized PC services were identified. Specialized services per population ranges from 0.09 per 100,000 inhabitants in Lebanon and Saudi Arabia, Qatar and Kuwait; to zero services in the Occupied Palestinian Territories. On average, opioid consumption was 2.40 mg/capita/year. National PC strategies were reported in nine countries. In six countries, PC is officially accredited either as a specialty or sub-specialty, and PC mandatory courses are implemented in 36% of medical schools and 46% of nursing schools. National PC associations were documented in six countries. A higher pattern of development was identified in Jordan, Kuwait, Saudi Arabia, Oman, Lebanon, Qatar. Conclusions Despite a higher development in the Arabian Peninsula, the region is characterised by a very low provision of specialized PC services and opioid consumption. Policy improvements represent an opportunity to improve access to PC

Family coordination in families who have a child with autism spectrum disorder

Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

A Pilot Study of Abnormal Growth in Autism Spectrum Disorders and Other Childhood Psychiatric Disorders

The aims of the current study were to examine whether early growth abnormalities are (a) comparable in autism spectrum disorders (ASD) and other childhood psychiatric disorders, and (b) specific to the brain or generalized to the whole body. Head circumference, height, and weight were measured during the first 19 months of life in 129 children with ASD and 59 children with non-ASD psychiatric disorders. Both groups showed comparable abnormal patterns of growth compared to population norms, especially regarding height and head circumference in relation to height. Thus abnormal growth appears to be related to psychiatric disorders in general and is mainly expressed as an accelerated growth of height not matched by an increase in weight or head circumference

Successful treatment of metastatic melanoma by adoptive transfer of blood-derived polyclonal tumor-specific CD4+ and CD8+ T cells in combination with low-dose interferon-alpha

A phase I/II study was conducted to test the feasibility and safety of the adoptive transfer of tumor-reactive T cells and daily injections of interferon-alpha (IFNα) in metastatic melanoma patients with progressive disease. Autologous melanoma cell lines were established to generate tumor-specific T cells by autologous mixed lymphocyte tumor cell cultures using peripheral blood lymphocytes. Ten patients were treated with on average 259 (range 38–474) million T cells per infusion to a maximum of six infusions, and clinical response was evaluated according to the response evaluation criteria in solid tumors (RECIST). Five patients showed clinical benefit from this treatment, including one complete regression, one partial response, and three patients with stable disease. No treatment-related serious adverse events were observed, except for the appearance of necrotic-like fingertips in one patient. An IFNα-related transient leucopenia was detected in 6 patients, including all responders. One responding patient displayed vitiligo. The infused T-cell batches consisted of tumor-reactive polyclonal CD8+ and/or CD4+ T cells. Clinical reactivity correlated with the functional properties of the infused tumor-specific T cells, including their in vitro expansion rate and the secretion of mainly Th1 cytokines as opposed to Th2 cytokines. Our study shows that relatively low doses of T cells and low-dose IFNα can lead to successful treatment of metastatic melanoma and reveals a number of parameters potentially associated with this success