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Following a period of slow progress, the completion of genome sequencing and the paradigm shift relative to the cell of origin for high grade serous ovarian cancer (HGSOC) led to a new perspective on the biology and therapeutic solutions for this deadly cancer. Experimental models were revisited to address old questions, and improved tools were generated. Additional pathways emerging as drivers of ovarian tumorigenesis and key dependencies for therapeutic targeting, in particular, VEGF-driven angiogenesis and homologous recombination deficiency, were discovered. Molecular profiling of histological subtypes of ovarian cancer defined distinct genetic events for each entity, enabling the first attempts toward personalized treatment. Armed with this knowledge, HGSOC treatment was revised to include new agents. Among them, PARP inhibitors (PARPis) were shown to induce unprecedented improvement in clinical benefit for selected subsets of patients. Research on mechanisms of resistance to PARPis is beginning to discover vulnerabilities and point to new treatment possibilities. This Review highlights these advances, the remaining challenges, and unsolved problems in the field. [ABSTRACT FROM AUTHOR]

This study constructs machine learning algorithms that are trained to classify samples using sound symbolism, and then it reports on an experiment designed to measure their understanding against human participants. Random forests are trained using the names of Pokémon, which are fictional video game characters, and their evolutionary status. Pokémon undergo evolution when certain in-game conditions are met. Evolution changes the appearance, abilities, and names of Pokémon. In the first experiment, we train three random forests using the sounds that make up the names of Japanese, Chinese, and Korean Pokémon to classify Pokémon into pre-evolution and post-evolution categories. We then train a fourth random forest using the results of an elicitation experiment whereby Japanese participants named previously unseen Pokémon. In Experiment 2, we reproduce those random forests with name length as a feature and compare the performance of the random forests against humans in a classification experiment whereby Japanese participants classified the names elicited in Experiment 1 into pre-and post-evolution categories. Experiment 2 reveals an issue pertaining to overfitting in Experiment 1 which we resolve using a novel cross-validation method. The results show that the random forests are efficient learners of systematic sound-meaning correspondence patterns and can classify samples with greater accuracy than the human participants. [ABSTRACT FROM AUTHOR]

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas. Author summary: Schistosomiasis is a neglected tropical disease, caused by the parasitic trematodes of the genus Schistosoma. Schistosomiasis is endemic to regions within Africa, Asia and South America with at least 250 million people infected and a further 779 million at risk of infection. The lifecycle of schistosomes are complex and involve specific freshwater intermediate snail hosts which shed infective cercariae into the waterbodies they inhabit. Schistosomiasis is subsequently transmitted to humans or animals that contact cercariae contaminated water. In Africa, human disease is largely caused by Schistosoma mansoni and Schistosoma haematobium. However, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform local environmental, food security and health programmes. To this end, we re-purposed a nucleic acid detection technology to enable the detection of different schistosome species. Our DNA-biosensor, abbreviated as 'SNAILS', employs carefully designed probes that recognise species-specific DNA sequences, coupled with enzymatic amplification steps, and a fluorescent signal-dye to indicate a positive detection. 'SNAILS' successfully differentiates between S. mansoni and S. haematobium samples and could conceivably be employed within future global health programmes. [ABSTRACT FROM AUTHOR]

A binary preference relation on a real vector space satisfying four (natural) axioms is shown to induce a utility function composed of a linear function to the reals and a weakly monotonic function. The key axiom is decomposition, and the utility function can be taken to be linear if and only if this axiom’s converse is also satisfied. Important consequences follow for risk-sensitive discounted Markov decision processes, decision trees, and the discounted utility model in economics. Since the four axioms imply that preferences correspond to discounting, the four axioms without the converse imply that preferences are consistent with discounting without risk neutrality. [ABSTRACT FROM AUTHOR]

Summary: Background: The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims: To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods: We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results: We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post‐treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate‐treated patients. Conclusions: Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments. [ABSTRACT FROM AUTHOR]

Sepsis is common and represents a major public health burden with significant associated morbidity and mortality. However, despite substantial advances in sepsis recognition and management in well-resourced health systems, there remains a distinct lack of research into sepsis in Africa. The lack of evidence affects all levels of healthcare delivery from individual patient management to strategic planning at health-system level. This is particular pertinent as African countries experience some of the highest global burden of sepsis. The 2017 World Health Assembly resolution on sepsis and the creation of the Africa Sepsis Alliance provided an opportunity for change. However, progress so far has been frustratingly slow. The recurrent Ebola virus disease outbreaks and the COVID-19 pandemic on the African continent further reinforce the need for urgent healthcare system strengthening. We recommend that African countries develop national action plans for sepsis which should address the needs of all critically ill patients. [ABSTRACT FROM AUTHOR]

The increasing use of geographic information systems (GIS) in everyday life is profoundly shaping how humans navigate and interact with their surroundings. Behavioural and ethnographic experimental research indicates that increased usage of GPS devices is having a significant impact on human neurocognitive systems, especially memory and perception (Gramann et al. 2017). Despite this, there has only been a limited investigation of the implications of the spread of GIS technologies. In this paper, we explore how habitual reliance on GPS technology undermines autonomous decision-making through "nudging" (Sunstein and Thaler 2008)—that is, the alteration of psychological behaviour without the explicit forbidding of choice. In particular, we make a novel distinction between what we refer to as "suggestive nudging"—the suggesting of certain routes to take to get to a destination—and "disclosure nudging"—the normalisation of constant tracking and disclosing of our locations to government and corporate actors. We shall argue that although suggestive and disclosure nudging are in principle separate, that in practice they are intertwined in the design of modern GPS devices. Additionally, since human spatial cognition is highly plastic and susceptible to being sculpted by cultural practices (Hutchins 1995; Levinson 2003), this exacerbates the negative implications of the 'in practice' link of suggestive and disclosure nudging by making the latter harder to avoid and opt-out of. We argue that this state of affairs necessitates re-designing GPS devices. [ABSTRACT FROM AUTHOR]

In this paper, we analyse how GPS-based navigation systems are transforming some of our intellectual virtues and then suggest two strategies to improve our practices regarding the use of such epistemic tools. We start by outlining the two main approaches in virtue epistemology, namely virtue reliabilism and virtue responsibilism. We then discuss how navigation systems can undermine five epistemic virtues, namely memory, perception, attention, intellectual autonomy, and intellectual carefulness. We end by considering two possible interlinked ways of trying to remedy this situation: [i] redesigning the epistemic tool to improve the epistemic virtues of memory, perception, and attention; and [ii] the cultivation of cognitive diligence for wayfinding tasks scaffolding intellectual autonomy and carefulness. [ABSTRACT FROM AUTHOR]

Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Simple Summary: Sampling stools from animals is a useful way of diagnosing diseases. Faeces contain large numbers of micro-organisms, including bacteria, and, to preserve these, farmers and owners are advised to store the stool samples in a fridge at 4 °C. However, in a farm setting, access to working onsite refrigeration is not guaranteed. This means that samples can often sit at ambient temperature for several days until they are sent to the laboratory for analysis, and these may be located at significant distances from the farms. Leaving faeces at room temperature can lead to a change in bacterial composition, which can result in bacterial overgrowth and difficulty in detecting certain species for diagnosis, such as Salmonella (S.) species. In this study, a commercially available animal stool storage kit was tested for its ability to chemically preserve bacterial DNA, without relying on cold storage. The kit successfully preserved Salmonella spp. in cow stool at room temperature. The success of kits such as this could enable the accurate diagnoses of bacterial disease where cold storage is not available. Stool sampling is a useful tool for diagnosing gastrointestinal disease in veterinary medicine. The sub-clinical disease burden of Salmonella spp. in cattle can become significant for farmers. However, current methods of faecal sampling in a rural setting for diagnosis are not consistently sufficient for the preservation of Salmonella spp. in faeces. This study evaluated the use of a commercial stool storage kit for bacterial preservation in cow faecal samples compared to unpreserved stools placed into refrigeration at different time-points. A stool sample was collected per-rectum from one apparently healthy Holstein–Freisen cow. The sample was weighed and aliquoted into two sterile Falcon tubes and into two commercial kit tubes. The aliquots were then placed into refrigeration at 4 °C at 0, 24, and 96 h after processing. One commercial kit tube was not aliquoted and remained at ambient temperature. After 2 weeks, DNA was extracted from the samples and analysed using endpoint PCR, revealing a sub-clinical infection with Salmonella spp. The bacterium was best preserved when the stool was stored in the commercial kit at ambient temperature and re-homogenised immediately prior to DNA extraction. The unpreserved stool did not maintain obvious levels of Salmonella spp. after 24 h at ambient temperature. This commercial kit should be considered for use in the diagnosis of salmonellosis in cattle. [ABSTRACT FROM AUTHOR]

The purpose of this report is to describe the case and management of an unexplained vitreous haemorrhage that occurred after repeated roller-coaster riding. The authors inadvertently demonstrate the value of observation over immediate surgery in certain situations and review the literature on vitreoretinal and other ocular complications after roller-coaster riding. A 26-year-old male presented 12 h after riding high-velocity roller-coasters with a left vitreous haemorrhage. A hazy view of the retina and B-scan revealed a bullous area of superior-temporal retinal lifting. A diagnosis of a presumed macula-on retinal detachment was made and the patient was listed for a pars plana vitrectomy retinal detachment repair. An abnormal clotting result, which was subsequently found out to be erroneous, ultimately delayed the procedure. During this delay the vision and retinal view improved to an extent whereby the diagnosis of a retinoschisis with an intraretinal cyst was made and surgery was avoided. The patient regained 6/6 vision, without the need to undergo surgery. Historically the management of an unexplained vitreous haemorrhage was observation with serial B-scans. The current evidence and practice for treating unexplained vitreous haemorrhage have since moved towards early surgical intervention. The authors highlight that despite the current trend, a place remains for conservative management for selected cases. [ABSTRACT FROM AUTHOR]

Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a-/- ptpn11b-/- zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a functional signaling role, requiring its catalytic activity and SH2 domains but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested that these processes occurred in ptpn11a-/- ptpn11b-/- zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a-mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration. [ABSTRACT FROM AUTHOR]

Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant ( ptena−/−ptenb−/−) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker junbb, appeared normal upon caudal fin-fold amputation of ptena−/−ptenb−/− zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration. [ABSTRACT FROM AUTHOR]

We prove that the group algebra KG of a group G over a field K is primitive, provided that G has a non-abelian free subgroup with the same cardinality as G , and that G satisfies the following condition ( ⁎ ) : for each subset M of G consisting of a finite number of elements not equal to 1, and for any positive integer m , there exist distinct a , b , and c in G so that if ( x 1 − 1 g 1 x 1 ) ⋯ ( x m − 1 g m x m ) = 1 , where g i is in M and x i is equal to a , b , or c for all i between 1 and m , then x i = x i + 1 for some i . This generalizes results of [1,9,17] , and [18] , and proves that, for every countably infinite group G satisfying ( ⁎ ) , KG is primitive for any field K . We use this result to determine the primitivity of group algebras of one relator groups with torsion. [ABSTRACT FROM AUTHOR]

Two-dimensional magnetic recording (TDMR) offers the opportunity to provide areal density (AD) gain, but questions were unanswered as to how the gain is achieved and what can be done to maximize the gain from this new technology. In this paper, we offer some reasons why different investigators might report different AD gain opportunities. We present data collected on a spin stand with two reader heads and processed with a commercially available field programmable gate array TDMR channel. The implications of this paper should provide guidelines on reader geometries, placement, and performance. [ABSTRACT FROM AUTHOR]

Given a one-parameter path of equations for which there is a trivial branch of solutions, to determine the points on the branch from which there bifurcate nontrivial solutions, there is the heuristic principle of linearization. That is to say, at each point on the branch, linearize the equation, and justify the inference that points on the branch that are bifurcation points for the path of linearized equations are also bifurcation points for the original path of equations. In quite general circumstances, for the bifurcation of critical points, we show that, at isolated singular points of the path of linearizations, a property of the path that is known to be sufficient to force bifurcation of nontrivial critical points is also necessary. To be more precise, let I be an open interval of real numbers that contains the point λ0 and B an open ball about the origin of a real, separable Hilbert space H. Let Ψ: I × B → R be a family of C2 functions. For λ ∊ I, assume ▿ xΨ(λ, 0) = 0, and set Hessianx Ψ(λ, 0) ≡ Lλ. Assume Lλ is invertible if λ ≠ λλ0 and Lλ0 is Fredholm. It is known that if the spectral flow of L: I → L(H) across λ0 is nonzero, then in each neighborhood of (λ0, 0) there are pairs (λ, x), x ≠ 0, for which ▿ xΨ(λ, x) = 0. We prove that if L: I → L(H) is a continuous path of symmetric operators for which Lλ is invertible for λ ≠ λ0, Lλ0 is Fredholm, and the spectral flow of L: I → L(H) across λ0 is zero, then there is an open interval J that contains the point λ0, an open ball B about the origin, and a family Ψ: J × B → R of C2 functions such that, for each λ ∊ J, ▿ xΨ(λ, 0) = 0 and Hessianx Ψ(λ, 0) = Lλ, but ▿ xΨ(λ, x) ≠ 0 if x ≠ 0. Therefore, at an isolated singular point of the path of linearizations of the gradient, under the sole further assumption that the linearization at the singular point is Fredholm, spectral flow is a complete invariant for the detection of bifurcation of nontrivial critical points. [ABSTRACT FROM AUTHOR]

Zr and its alloys are widely used in multiple areas, including the nuclear and medical fields. Previous studies indicate that a ceramic conversion treatment (C2T) of Zr-based alloys can address the issues of low hardness, high friction, and poor wear resistance of Zr based alloys. This paper introduced a novel catalytic ceramic conversion treatment (C3T) to Zr702 by pre-depositing a catalytic film (such as silver, gold, platinum, etc.) before the ceramic conversion treatment, which efficiently promoted the C2T process, in terms of reduced treatment times, with a thick, good quality, surface ceramic layer. The formed ceramic layer significantly improved the surface hardness and tribological properties of Zr702 alloy. Compared with conventional C2T, the C3T technique provided two orders of magnitude reduction of wear factor and reduced the coefficient of friction from 0.65 to <0.25. Among the C3T samples, the C3TAg and the C3TAu samples have the highest wear resistance and lowest CoF, mainly due to the self-lubricant formation during the wear processes. [ABSTRACT FROM AUTHOR]

The article presents a report on polio elimination activities in Afghanistan and Pakistan from January 2013 to August 2014. Topics include the implementation of the Polio Eradication and Endgame Strategic Plan for 2013 to 2018, the use of oral poliovirus vaccine (OPV3) on infants in both countries, and the inaccessibility of children in Federally Administered Tribal Areas (FATA). It also discusses acute flaccid paralysis (AFP) and environmental surveillance for wild poliovirus (WPV) presence.

Electric drive systems, which include electric machines and power electronics, are a key enabling technology for advanced vehicle propulsion systems that reduce the petroleum dependence of the ground transportation sector. To have significant effect, electric drive technologies must be economical in terms of cost, weight, and size while meeting performance and reliability expectations. This paper will provide details of the design, analysis, and testing of an advanced interior permanent magnet (PM) machine that was developed to meet the FreedomCAR 2020 specifications. The 12-slot/10-pole machine has segmented stator structure equipped with fractional-slot nonoverlapping concentrated windings. The rotor has a novel spoke structure/assembly. Several prototypes with different thermal management schemes have been built and tested. This paper will cover the test results for all these prototypes and highlight the tradeoffs between the various schemes. Due to the high machine frequency ( $\sim$1.2 kHz at the top speed), detailed analysis of various loss components and ways to reduce them will be presented. In addition, due to the high coolant inlet temperature and the fact that the machine is designed to continuously operate at 180 ^\circ\C, detailed PM demagnetization analysis will be presented. The key novelty in this paper is the advanced rotor structure and the thermal management schemes. [ABSTRACT FROM AUTHOR]

The article reports on the progress toward the eradication of polio in Afghanistan through vaccination between January 2012 to September 2013. It says that nine cases of indigenous wild poliovirus (WPV 1) were confirmed during the period. It adds that no WPV 1 cases have been reported from the main WPV reservoir, the Southern Region, since November 2012, while all 9 cases were in the Eastern Region and caused by the WPV that originated from Pakistan.

Tim Jordan provides a nuanced view: it is the digital I practices i that these companies enact that form the digital economy. He weaves together an optimistic critique of prior examinations of the digital economy, while suggesting that the key to understanding digital economies is to examine how "the digital" subtly reinforces or disrupts existing systems of labour, profit, and control. Viewing digital economies and communities through the lens of practices rather than companies enables much broader investigations of digital markets and communities. [Extracted from the article]

Titanium oxide layers were produced via a novel catalytic ceramic conversion treatment (CCCT, C3T) on Ti-6Al-4V. This CCCT process is carried out by applying thin catalytic films of silver and palladium onto the substrate before an already established traditional ceramic conversion treatment (CCT, C2T) is carried out. The layers were characterised using scanning electron microscopy, X-ray diffraction, transmission electron microscopy; surface micro-hardness and reciprocating tribological performance was assessed; antibacterial performance was also assessed with S. aureus. This CCCT has been shown to increase the oxide thickness from ~5 to ~100 µm, with the production of an aluminium rich layer and agglomerates of silver and palladium oxide surrounded by vanadium oxide at the surface. The wear factor was significantly reduced from ~393 to ~5 m3/N·m, and a significant reduction in the number of colony-forming units per ml of Staphylococcus aureus on the CCCT surfaces was observed. The potential of the novel C3T treatment has been demonstrated by comparing the performance of C3T treated and untreated Ti6Al4V fixation pins through inserting into simulated bone materials. [ABSTRACT FROM AUTHOR]

Background. Oral poliovirus vaccine (OPV) has not been used in the United States since 2000. Type 1 vaccine-derived poliovirus (VDPV) was identified in September 2005, from an unvaccinated Amish infant hospitalized in Minnesota with severe combined immunodeficiency. An investigation was conducted to determine the source of the virus and its means of transmission. Methods. The infant was tested serially for poliovirus excretion. Investigations were conducted to detect poliovirus infections or paralytic poliomyelitis in Amish communities in Minnesota, neighboring states, and Ontario, Canada. Genomic sequences of poliovirus isolates were determined for phylogenetic analysis. Results. No source for the VDPV could be identified. In the index community, 8 (35%) of 23 children tested, including the infant, had evidence of type 1 poliovirus or VDPV infection. Phylogenetic analysis suggested that the VDPV circulated in the community for ~2 months before the infant's infection was detected and that the initiating OPV dose had been given before her birth. No paralytic disease was found in the community, and no poliovirus infections were found in other Amish communities investigated. Conclusions. This is the first demonstrated transmission of VDPV in an undervaccinated community in a developed country. Continued vigilance is needed in all countries to identify poliovirus infections in communities at high risk of poliovirus transmission. [ABSTRACT FROM AUTHOR]

Abstract: While control of intracellular pathogens, such as the protozoan Leishmania, is dependent on the generation of type-1 immune responses, the role of T helper 2 cytokines in the disease process is more controversial. Traditionally these cytokines were perceived as counter-regulating type-1 responses and promoting disease exacerbation. Nevertheless a substantial body of evidence now exists suggesting that the development of effective type-1 immunity can involve the significant involvement of the Th2 cytokines IL-4 and IL-13. This article reviews, using Leishmania species in particular, the circumstances under which these cytokines can promote protective type-1 immunity. [Copyright &y& Elsevier]

The article considers the validity of the jurisdiction-stripping of the provisions of the Military Commissions Act of 2006 (MCA) and Detainee Terror Act of 2005 (DTA) in the U.S. First, it considers whether the statutory review in the Washington D.C. Circuit allowed by the MCA and DTA is a constitutionally adequate substitute. Possible alternative avenues to judicial review are considered. Third, it deals whether the MCA's repeal of jurisdiction over detainees' claims of unconstitutional custody and treatment violates the Suspension Clause (SC) or the Exceptions and Regulations Clause. Finally, it deals the contention that neither the SC nor any other rights under the Constitution protect noncitizens held outside the U.S. Other significant analyses relative to the matter are presented.

The article features the new world screwworm fly (NWSFs) and old world screwworm fly (OWSFs). It offers information on the history, latest status of NWSF populations, incursions of NWSFs into the Western Hemisphere, incursions of NWSFs into the Eastern Hemisphere, areas from which the species has been eradicated in the Western Hemisphere, developments in the detection of screwworms and prevention of infestation and recent development involving OWSFs in the Middle East.

Presents a solution to the problem of finding the motion of the point where the water hits the wall in a situation involving the spraying of a wall with a garden hose. Focus on the position of the splash point rather than the velocity; Development of the behavior of the splash point; Use of the mathematics of inverse functions.

CD8+ T cells are essential for long-term, vaccine-induced resistance against intracellular pathogens. Here we show that natural antibodies, acting in concert with complement, are endogenous adjuvants for the generation of protective CD8+ T cells after vaccination against visceral leishmaniasis. IL-4 was crucial for the priming of vaccine-specific CD8+ T cells, and we defined the primary source of IL-4 as a CD11b+CD11clo phagocyte. IL-4 secretion was not observed in antibody-deficient mice and could be reconstituted with serum from normal, but not Btk immune-deficient, mice. Similarly, no IL-4 response or CD8+ T-cell priming was seen in C1qa-/- mice. These results identify a new pathway by which immune complex-mediated complement activation can regulate T-cell-mediated immunity. We propose that this function of natural antibodies could be exploited when developing new vaccines for infectious diseases. [ABSTRACT FROM AUTHOR]

Explicit formulae for rational Lusternik–Schnirelman (L–S) category (cat0) are rare, but some are available for a class of spaces which includes homogeneous spaces G/H when H is a product of at most 3 rank 1 groups, and rank G−rank H&les;1. We extend the applicability of these formulae to the case when rank G=5 and H is a 4-torus or (SU2)4. With a Sullivan minimal model as data, implementing the formula requires the selection of a regular subsequence of length 4 from a sequence f1,…,f5 of homogeneous polynomials in 4 variables satisfyingdim Q[x1,…,x4]/(f1,…,f5)<∞.Such subsequences are readily obtainable, and the ease of computation is in contrast to most available methods for determining rational L–S category, which usually involve both upper and lower bounds and a good measure of luck.The proof of the formula is a pretty application of ideal class groups in algebraic topology. We also present some examples to illustrate our result. [Copyright &y& Elsevier]

Discusses a study that evaluated the effects of aging on cardiac rhythm while mountain climbing at high altitude. Description of the climb to Mount Kilimanjaro; Hourly numbers of left ventricular ectopic complexes and levels of blood oxygen saturation while climbing; Blood pressure levels during rest and sleep at increasing altitude.

Examines national hospital charge data, vital statistics and etiologic studies of adult pneumonia hospitalizations and Medicare cost data to estimate the morbidity, mortality and medical costs of respiratory syncytial virus (RSV)-associated pneumonia among the elderly in the United States. Medical and economic burden imposed by the RSV-associated pneumonia among the elderly in the U.S.; Implications.

Presents research in which methods of optimal control were used to calculate minimal distance paths between prescribed initial and final configurations of a wheeled mobile robot. Discussion on obstacle avoidance for wheeled robots; Explanation of research methods utilized; Description of a wheeled robot.

Explores questions about the telegraph that have not heretofore been posed-- at least systematically. The practices and activities that could not have been undertaken without it; Price and quantity data; Logistical control in the railroad sector;Inventory savings in manufacturing and distribution; Conclusion.

The question of whether increased reading fluency is associated with an increased dependence on context in the process of word recognition was examined. Goodman (1965) concluded that this is indeed the case. In a similar study, Nicholson (1991) arrived at the opposite conclusion, finding that increased use of context is associated with less reading skill. In the current study, Goodman's data were reanalyzed, and his procedure was repeated with 42 children in Grades 1-3. Reading fluency was not significantly associated with use of context. [ABSTRACT FROM AUTHOR]

Examines the effect of the collapse of the Soviet Union state to the Russian people. Examination of the Russian political culture in the post-Soviet period; Redevelopment of the triple transition technique; Effects of the radical redefinition of the Soviet state; Political, economic and social concerns of Syktyvkar and Kirov residents.

The Echo Lake intrusion in the Upper Peninsula (UP) of Michigan, USA, was formed during the 1.1 Ga Midcontinent Rift event in North America. Troctolite is the predominant rock unit in the intrusion, with interlayered bands of peridotite, mafic pegmatitic rock, olivine gabbro, magnetite-bearing gabbro, and anorthosite. Exploratory drilling has revealed a platinum group element (PGE)-enriched zone within a 45 m thick magnetite-ilmenite-bearing olivine gabbro unit with grades up to 1.2 g/t Pt + Pd and 0.3 wt. % Cu. Fine, disseminated grains of sulfide minerals such as pyrrhotite and chalcopyrite occur in the mineralized interval. Formation of Cu-PGE-rich sulfide minerals might have been caused by sulfide melt saturation in a crystallizing magma, which was triggered by a sudden decrease in fO2 upon the crystallization and separation of titaniferous magnetite. This PGE-enriched zone is comparable to other well-known reef-like PGE deposits, such as the Sonju Lake deposit in northern Minnesota. [ABSTRACT FROM AUTHOR]

The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies. In this article, we explore the host-chemotherapeutic microbiota axis, from basic science to clinical research, and describe how it may change the face of cancer treatment. [ABSTRACT FROM AUTHOR]

A response from the author of the article "A Novel ‘Dilute-and-Shoot' Liquid Chromatography–Tandem Mass Spectrometry Method for the Screening of Antihypertensive Drugs in Urine" in the 2016 issue is presented.

Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota's functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson's coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota. [ABSTRACT FROM AUTHOR]

The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5-6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research. Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers--such as lung and urogenital tract--was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics. On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a 'healthy' microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite 'interactome' between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may be exploited for therapeutic benefit in cancer and the safety implications of performing such research in oncology patients. [ABSTRACT FROM AUTHOR]

Provides an overview of the book "Russian Regions and Regionalism: Strength Through Weakness," edited by Graeme P. Herd and Anne Aldis.

On 7 June 2021, Juno crossed the orbital path of Jupiter's moon Ganymede, flying within 1,046 km of the surface. Juno's low‐light‐sensitive Stellar Reference Unit (SRU) navigation camera captured an image of the satellite's dark side in a region of Xibalba Sulcus illuminated solely by Jupiter‐shine. Collected at high incidence angle with 670–920 m/pixel resolution, the image reveals terrain morphology, ejecta, and numerous small craters that cannot be discerned in the Voyager imagery used for the USGS global geologic map of Ganymede. The Juno data enable improved mapping of Ganymede's surface and reinterpretation of material and crater ages in a region previously characterized as light "undivided" material due to poor image resolution. The illumination conditions achieved by the SRU observation geometry also reveal the detailed morphology of a 270‐km elongated bright feature in this area. These newly resolved features contribute to an improved understanding of Ganymede's complex history. Plain Language Summary: On 7 June 2021, the Juno spacecraft flew within about 1,000 km of the surface of Jupiter's largest moon, Ganymede. The Mission used their sensitive navigation camera to photograph the moon's dark side where it was lit only by scattered sunlight from Jupiter. This new imaging approach revealed multiple surface features, including a patchwork of different surface textures (such as grooved terrain), several craters, and ejecta deposits. These features had not been visible in images collected by previous spacecraft. Well‐resolved details of the surface structure help us understand Ganymede's history and the processes responsible for how it appears today. One feature may either be ejecta from a very distant crater or scars from the pieces of a broken up comet that collided with Ganymede. Key Points: Juno's Stellar Reference Unit imaged Ganymede at high resolution and incidence angle while the surface was illuminated by Jupiter‐shineGrooved material, ejecta, and multiple craters are now resolved, enabling improved mapping of a 2 × 105 km2 region in Xibalba SulcusThe unique morphology of a possible 270‐km scar from comet fragments, or a highly isolated distal ray from Tros, is revealed [ABSTRACT FROM AUTHOR]