New results from testing relativistic gravity with radio pulsars

We experience a golden era in testing and exploring relativistic gravity. Whether it is results from gravitational-wave detectors, satellite or lab experiments, radio astronomy plays an important complementary role. Here, one can mention the cosmic microwave background, black hole imaging and, obviously, binary pulsars. This talk will concentrate on the latter and new results from studies of strongly self-gravitating bodies with unrivalled precision. This presentation compares the results to other methods, discusses implications for other areas of relativistic astrophysics and will give an outlook of what we can expect from new instruments in the near future.

Chopinowskie narracje z „dziecięcego pokoju”. Mistrz w czasopismach i publikacjach dla najmłodszych w XIX wieku – rekonesans

The article discusses the biographical accounts and stories about Frédéric Chopin published in the most representative children’s magazines of the turn of the twentieth century: Wieczory Rodzinne (Family evenings), Przyjaciel Dzieci (Children’s friend) and Moje Pisemko (My little magazine). A kind of complementary role to them is played by the analysis of Janina Sedlaczkówna’s 1891 book Dwaj mistrze: opowiadanie o życiu Artura Grottgera i Fryderyka Chopina (Two maestros: a story about the lives of Artur Grottger and Frédéric Chopin) and Teresa Jadwiga Papi’s stories from 1898 of the same title Dwaj mistrze (Two maestros) about Chopin and Moniuszko. The collected comments and conclusions are presented in relation to twentieth- century biographical texts about Chopin.

Politics, Policy, and Crime Ethnography

This chapter encourages social scientists, policy planners, and public administrators to reflect critically on the methods used to define crime problems and policy responses to them. It argues for the increased use of ethnographic methods in formulating policy by seeking points of connection with quantitative approaches. Quantitative methods are better suited for crime policy given their methodological rigor, instrumental and programmatic orientation, and relatively low costs per datum unit. However, qualitative methods have a complementary role to play, being better attuned to the subjective experiences of crime and crime control and better able to illustrate factors correlated with these phenomena. Ethnographic methods permit reflexivity regarding the broader settings and specific contexts of crime and criminological research. Two cases of ethnographic techniques within criminal justice practice are shared to demonstrate their viability—one from the US Department of Justice and another from Court Watch Poland. The chapter finishes with lessons for researchers and policy planners, including the importance of engaging in collaborative research, triangulating methods, embracing uncomfortable findings, and reconsidering research ethics.

THO and TRAMP complexes prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions

Expansion of structure-forming CAG/CTG repetitive sequences is the cause of several neurodegenerative disorders and deletion of repeats is a potential therapeutic strategy. Transcription-associated mechanisms are known to cause CAG repeat instability. In this study, we discovered that Thp2, an RNA export factor and member of the THO complex, and Trf4, a key component of the TRAMP complex involved in nuclear RNA degradation, are necessary to prevent CAG fragility and repeat contractions in a S. cerevisiae model system. Depletion of both Thp2 and Trf4 proteins causes a highly synergistic increase in CAG repeat fragility, indicating a complementary role of the THO and TRAMP complexes in preventing genome instability. Loss of either Thp2 or Trf4 causes an increase in RNA polymerase stalling at the CAG repeats and genome-wide transcription-replication conflicts (TRCs), implicating impairment of transcription elongation as a cause of CAG fragility and instability in their absence. Analysis of the effect of RNase H1 overexpression on CAG fragility and TRCs suggests that co-transcriptional R-loops are the main cause of CAG fragility in the thp2Δ mutants. In contrast, CAG fragility and TRCs in the trf4Δ mutant can be compensated for by RPA overexpression, suggesting that excess unprocessed RNA in TRAMP4 mutants leads to reduced RPA availability and high levels of TRCs. Our results show the importance of RNA surveillance pathways in preventing RNAPII stalling, TRCs, and DNA breaks, and show that RNA export and RNA decay factors work collaboratively to maintain genome stability.

Trends in Informal and Formal Long-Term Care Use Among Older Adults With Disabilities in Japan

Whether increased formal long-term care (LTC) reduces informal LTC use by serving as a substitute or has a complementary role that boosts both informal and formal LTC use has been an important issue for evaluating LTC policy effectiveness. We described trends in in-home LTC use among older adults and LTC availability in relation to changes in LTC policy in Japan. In addition, we examined whether these trends differ by living arrangements, gender, income, and disability levels. We used five waves of repeated cross-sectional data starting in 1999 to 2017. The use of both informal and formal LTC types combined increased until 2006 and then gradually decreased while remaining higher than in 1999. Although implementing the LTC program may have temporarily contributed to the complementary use of both LTC types, eligibility limitations brought about by LTC reform potentially reduced the effects of formal LTC’s complementary role.

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4 and B.1.1.222 or B.1.1.519 and the nucleocapsid mutation S194L associated with symptoms

Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1–S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

The Role of Antigen Rapid Diagnostic Test in COVID-19 Diagnosis

Since the emergence of a novel infection due to the SARS-CoV-2 virus (COVID-19), the World Health Organization has urged countries to develop diagnostic tests to combat the pandemic. Molecular assays were developed following the release of the gene sequence of the virus in January 2020. Reverse transcription-quantitative PCR (RT-qPCR) is taken as the gold standard for the diagnosis of COVID-19. However, due to its limitations, highly sensitive methods for detecting antigens (antigen rapid diagnostic tests) have been developed that would help in a timely and accurate diagnosis. Antigen rapid diagnostic tests (Ag-RDTs) can help guide patient management at the point of care by random screening, re-testing, and timely decision-making in the field of public health. When the affordability and validity of the diagnostic assay are involved, no assay can show 100% correct results. Further studies need to be done to better understand the response of the Ag-RDTs in different settings. Nevertheless, Ag-RDTs can play a complementary role in the response and case management of COVID-19.

The cost-effectiveness of physician assistants/associates: A systematic review of international evidence

Background The global utilization of the physician assistant/associate (PA) is growing. Their increasing presence is in response to the rising demands of demographic changes, new developments in healthcare, and physician shortages. While PAs are present on four continents, the evidence of whether their employment contributes to more efficient healthcare has not been assessed in the aggregate. We undertook a systematic review of the literature on PA cost-effectiveness as compared to physicians. Cost-effectiveness was operationalized as quality, accessibility, and the cost of care. Methods and findings Literature to June 2021 was searched across five biomedical databases and filtered for eligibility. Publications that met the inclusion criteria were categorized by date, country, design, and results by three researchers independently. All studies were screened with the Risk of Bias in Non-randomised Studies—of Interventions (ROBIN-I) tool. The literature search produced 4,855 titles, and after applying criteria, 39 studies met inclusion (34 North America, 4 Europe, 1 Africa). Ten studies had a prospective design, and 29 were retrospective. Four studies were assessed as biased in results reporting. While most studies included a small number of PAs, five studies were national in origin and assessed the employment of a few hundred PAs and their care of thousands of patients. In 34 studies, the PA was employed as a substitute for traditional physician services, and in five studies, the PA was employed in a complementary role. The quality of care delivered by a PA was comparable to a physician’s care in 15 studies, and in 18 studies, the quality of care exceeded that of a physician. In total, 29 studies showed that both labor and resource costs were lower when the PA delivered the care than when the physician delivered the care. Conclusions Most of the studies were of good methodological quality, and the results point in the same direction; PAs delivered the same or better care outcomes as physicians with the same or less cost of care. Sometimes this efficiency was due to their reduced labor cost and sometimes because they were more effective as producers of care and activity.

Complementary Role of Oxytocin and Vasopressin in Cardiovascular Regulation

The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.

Colorectal cancer and the blood loss paradox

BackgroundFaecal occult blood (FOB) positivity and iron deficiency anaemia (IDA) are common manifestations of colorectal cancer (CRC) and both potentially facilitate diagnosis at an earlier, more treatable stage. It has been assumed that both are the consequence of low-grade blood loss from the tumour bed.MethodA retrospective analysis of 1121 cases of CRC diagnosed at a single centre between 2010 and 2016, comparing cases presenting via FOB-based Bowel Cancer Screening Programme (BCSP) and IDA pathways for a series of variables including age, sex, tumour location and prevalence of anaemia.ResultsThe BCSP and IDA pathways each accounted for about 15% of the total case load. There were significant differences between the BCSP and IDA sub-groups in median age (68 vs 78 years: p<0.001), median haemoglobin (138 vs 89 g/L: p<0.001) and proportion of lesions in right colon (31.1% vs 82.5%: p<0.001). The major disparity in the prevalence of anaemia (overall 20.0% vs 98.2%: p<0.001) persisted when controlled for tumour location.ConclusionParadoxically, CRC screening through the detection of FOB positivity and IDA identifies distinctly different sub-populations of cases. The theoretical implication is that an additional mechanism may be required to explain the development of IDA in CRC. The practical implication is that detection of IDA may have a complementary role to the BCSP in population screening for CRC.