Antibiotic exposure within six months before systemic therapy was associated with lower cancer survival.

OBJECTIVES: The objective of the study was to quantify associations between cancer survival and antibiotic exposure before systemic anticancer therapy. STUDY DESIGN AND SETTING: This population-based cohort study compares cause-specific survival according to antibiotic exposure before non-immune checkpoint inhibitor (ICI) systemic therapy in patients diagnosed with single primary cancers in New South Wales between 2013 and 2016. Proportional hazards regression was used to control for confounding, with no antibiotic exposure in the six months before non-ICI systemic therapy serving as the comparator. RESULTS: After adjusting for tumour spread, cancer site, age, sex and comorbidity, people having antibiotic exposure within 180 days before non-ICI systemic therapy had poorer cancer survival (hazard ratios ranging from 1.21 [95% confidence interval: 1.06-1.39] to 1.58 [1.34-1.87]) for shorter periods since antibiotic exposure (P < .0001). Similarly, poorer survival trends applied for localized and metastatic cancer. Of six prevalent cancers studied, lung and breast primaries showed the strongest associations of lower survival with prior antibiotic exposure. CONCLUSION: Antibiotic exposure within 180 days before non-ICI systemic cancer treatment is associated with poorer survival. If confirmed in other studies, it provides another reason for vigilant antibiotic stewardship

Reinventing residual reserves in the sea: Are we favouring ease of establishment over need for protection?

© 2014 The Authors. As systems of marine protected areas (MPAs) expand globally, there is a risk that new MPAs will be biased toward places that are remote or unpromising for extractive activities, and hence follow the trend of terrestrial protected areas in being 'residual' to commercial uses. Such locations typically provide little protection to the species and ecosystems that are most exposed to threatening processes. There are strong political motivations to establish residual reserves that minimize costs and conflicts with users of natural resources. These motivations will likely remain in place as long as success continues to be measured in terms of area (km2) protected. The global pattern of MPAs was reviewed and appears to be residual, supported by a rapid growth of large, remote MPAs. The extent to which MPAs in Australia are residual nationally and also regionally within the Great Barrier Reef (GBR) Marine Park was also examined. Nationally, the recently announced Australian Commonwealth marine reserves were found to be strongly residual, making almost no difference to 'business as usual' for most ocean uses. Underlying this result was the imperative to minimize costs, but without the spatial constraints of explicit quantitative objectives for representing bioregions or the range of ecological features in highly protected zones. In contrast, the 2004 rezoning of the GBR was exemplary, and the potential for residual protection was limited by applying a systematic set of planning principles, such as representing a minimum percentage of finely subdivided bioregions. Nonetheless, even at this scale, protection was uneven between bioregions. Within-bioregion heterogeneity might have led to no-take zones being established in areas unsuitable for trawling with a risk that species assemblages differ between areas protected and areas left available for trawling. A simple four-step framework of questions for planners and policy makers is proposed to help reverse the emerging residual tendency of MPAs and maximize their effectiveness for conservation. This involves checks on the least-cost approach to establishing MPAs in order to avoid perverse outcomes

The hand of Homo naledi

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like wrist and palm indicate a significant degree of climbing, despite the derived nature of many aspects of the hand and other regions of the postcranial skeleton in H. naledi

Stime di emissioni di inquinanti provenienti da sorgenti di traffico nell’area veneziana.

Purpose: Wnt signalling has been implicated in breast cancer, and in particular aberrant β-catenin-independent Wnt signalling has been associated with breast cancer metastasis and Tamoxifen resistance. Despite Wnt pathway involvement in many human cancers, attempts to target the pathway therapeutically have been disappointing. The recent discovery that the receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a novel Wnt receptor provides a potential new therapeutic and diagnostic target

Participatory social network map making with family carers of people living with dementia

This article focuses on the use of a participatory social network mapping method with family carers. This is one of a suite of methods developed in a 5-year qualitative multi-centre project exploring how neighbourhoods support, enable or disable people with dementia and their families to live well in their communities. The article considers how mapping provides insights into family support networks, revealing the fluidity of support and care within relationships as well as providing opportunity for individuals to represent the complexities of their relationships with more and less significant others. However, the potential offered by the approach goes beyond those of visual representations of networks and contacts. Paying attention to the co-production process, as well as the reflexive dialogue that emerges in the exchange between researcher, participants, and the maps themselves, we consider how the maps emerge as affective artifacts, weighted with emotion

Receptor protein tyrosine phosphatases are novel components of the polycystin complex

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of PKD1 and PKD2 that encode polycystin-1 and polycystin-2. Polycystin-1 is tyrosine phosphorylated and modulates multiple signaling pathways including AP-1, and the identity of the phosphatases regulating polycystin-1 are previously uncharacterized. Here we identify members of the LAR protein tyrosine phosphatase (RPTP) superfamily as members of the polycystin-1complex mediated through extra- and intracellular interactions. The first extracellular PKD1 domain of polycystin-1 interacts with the first Ig domain of RPTPσ, while the polycystin-1 C-terminus of polycystin-1 interacts with the regulatory D2 phosphatase domain of RPTPγ. Additional homo- and heterotypic interactions between RPTPs recruit RPTPδ. The multimeric polycystin protein complex is found localised in cilia. RPTPσ and RPTPδ are also part of a polycystin-1/E-cadherin complex known to be important for early events in adherens junction stabilisation. The interaction between polycystin-1 and RPTPγ is disrupted in ADPKD cells, while RPTPσ and RPTPδ remain closely associated with E-cadherin, largely in an intracellular location. The polycystin-1 C-terminus is an in vitro substrate of RPTPγ, which dephosphorylates the c-Src phosphorylated Y4237 residue and activates AP1-mediated transcription. The data identify RPTPs as novel interacting partners of the polycystins both in cilia and at adhesion complexes and demonstrate RPTPγ phosphatase activity is central to the molecular mechanisms governing polycystin-dependent signaling. This article is part of a Special Issue entitled: Polycystic Kidney Disease

Antidepressant and antipsychotic drug prescribing and diabetes outcomes: A systematic review of observational studies

AIMS: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. METHODS: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. RESULTS: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. CONCLUSIONS: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Contribution of nuclear texture analysis for the differential diagnosis of follicular lesions of the thyroid: comparison to immunohistochemical markers

Objective and methods: To investigate the utility of nuclear chromatin texture assessment in the differential diagnosis of follicular patterned lesions, by means of examining 76 samples previously submitted to the immunohistochemical protein analysis of HBME-1, CK-19 and galectina-3. Results: HBME-1 confirmed to be the most sensitive marker of malignancy. A series of morphometric, densitometric and texture variables were useful in the discrimination of the different types of follicular lesions. Among these variables, r(2), a parameter related to the granularity of the nucleus presented the best accuracy, sensitivity, specificity and positive and negative predictive values, distinguishing benign from malignant lesions. Conclusion: The morphometric analysis of nuclear chromatin images may add accuracy to the differential diagnosis of follicular patterned lesions. Arq Bras Endocrinol Metab. 2009;53(7):804-10.53780481