Researchers on ice? How the COVID-19 pandemic has impacted Antarctic researchers

The COVID-19 pandemic and pandemic-related measures have impacted the lives and work-related activities of Antarctic researchers. To explore these impacts, we designed, piloted and disseminated an online survey in English, Russian, Spanish and Chinese in late 2020 and early 2021. The survey explored how the pandemic affected the productivity of Antarctic researchers, their career prospects and their mental wellbeing. Findings exposed patterns of inequities. For instance, of the 406 unique responses to the survey, women appeared to have been affected more adversely than men, especially in relation to mental health, and early-career researchers were disadvantaged more than their mid- or late-career colleagues. Overall, a third of the research participants reported at least one major negative impact from the pandemic on their mental health. Approximately half of the participants also mentioned that the COVID-19 pandemic had some positive effects, especially in terms of the advantages that working from home brought and opportunities to attend events, network or benefit from training workshops online. We conclude with a series of recommendations for science administrators and policymakers to mitigate the most serious adverse impacts of the pandemic on Antarctic research communities, with implications for other contexts where scientific activities are conducted under extreme circumstances

The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation

Background: Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety. Aims of the research: The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men\u27s experience and acceptability of testosterone replacement therapy. Design: Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis. Data sources: Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications. Methods: We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages. Results: We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; p = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men\u27s lives and their experience of treatment. The cost-effectiveness of testosterone replacement therapy was dependent on whether uncertain effects on all-cause mortality were included in the model, and on the approach used to estimate the health state utility increment associated with testosterone replacement therapy, which might have been driven by improvements in symptoms such as sexual dysfunction and low mood. Limitations: A meaningful evaluation of mortality was hampered by the limited number of defined events. Definition and reporting of cardiovascular and cerebrovascular events and methods for testosterone measurement varied across trials. Conclusions: Our findings do not support a relationship between testosterone replacement therapy and cardiovascular/cerebrovascular events in the short-to-medium term. Testosterone replacement therapy improves sexual function and quality of life without adverse effects on blood pressure, serum lipids or glycaemic markers. Future work: Rigorous long-term evidence assessing the safety of testosterone replacement therapy and subgroups most benefiting from treatment is needed. Study registration: The study is registered as PROSPERO CRD42018111005. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/68/01) and is published in full in Health Technology Assessment; Vol. 28, No. 43. See the NIHR Funding and Awards website for further award information.Testosterone is a hormone which is vital for sexual activity, bone growth and muscle development in men. Men with low testosterone levels may experience problems with erections and may suffer from brittle bones (osteoporosis), weakness, feeling down (low mood) and tiredness. The manifestations of low testosterone can be treated with testosterone replacement therapy. However, there is current uncertainty about the positive effects of testosterone replacement therapy and its safety. We brought together results from all available medical studies that looked at the use of testosterone replacement therapy in men with low testosterone and contacted the doctors who led these studies to gather further information on their participants. We found 35 studies (5601 participants) conducted in different countries, 17 of which provided additional information on their participants. We did not find any evidence to show that testosterone replacement therapy increases the risk of heart problems, or any evidence to show that some men who take testosterone replacement therapy benefit more than others. Men with low testosterone reported having low mood, poor concentration and lack of energy; however, medical studies often failed to prove that these manifestations improved with testosterone replacement therapy. Most medical studies were conducted among white men in North America using questionnaires designed specifically for them; therefore, the results may not reflect the experiences of men in other countries and from more diverse ethnic backgrounds. There is too much uncertainty about the benefits of testosterone replacement therapy to accurately estimate its value for money for the NHS. We think our findings offer some reassurance to doctors and patients that testosterone replacement therapy does not increase the risk of heart problems. New studies are needed to find out whether some groups of men (such as older or younger men) are more likely to benefit from testosterone replacement therapy more than others. It is also important to develop tools which better reflect the experience of men from a diverse range of social and ethnic backgrounds. To inform men with low testosterone about our findings, we are creating a website with dedicated YouTube video clips

Single-atom imaging of fermions in a quantum-gas microscope

Single-atom-resolved detection in optical lattices using quantum-gas microscopes has enabled a new generation of experiments in the field of quantum simulation. Fluorescence imaging of individual atoms has so far been achieved for bosonic species with optical molasses cooling, whereas detection of fermionic alkaline atoms in optical lattices by this method has proven more challenging. Here we demonstrate single-site- and single-atom-resolved fluorescence imaging of fermionic potassium-40 atoms in a quantum-gas microscope setup using electromagnetically-induced-transparency cooling. We detected on average 1000 fluorescence photons from a single atom within 1.5s, while keeping it close to the vibrational ground state of the optical lattice. Our results will enable the study of strongly correlated fermionic quantum systems in optical lattices with resolution at the single-atom level, and give access to observables such as the local entropy distribution and individual defects in fermionic Mott insulators or anti-ferromagnetically ordered phases.Comment: 7 pages, 5 figures; Nature Physics, published online 13 July 201

Complex Interplay of Evolutionary Forces in the ladybird Homeobox Genes of Drosophila melanogaster

Tandemly arranged paralogous genes lbe and lbl are members of the Drosophila NK homeobox family. We analyzed population samples of Drosophila melanogaster from Africa, Europe, North and South America, and single strains of D. sechellia, D. simulans, and D. yakuba within two linked regions encompassing partial sequences of lbe and lbl. The evolution of lbe and lbl is highly constrained due to their important regulatory functions. Despite this, a variety of forces have shaped the patterns of variation in lb genes: recombination, intragenic gene conversion and natural selection strongly influence background variation created by linkage disequilibrium and dimorphic haplotype structure. The two genes exhibited similar levels of nucleotide diversity and positive selection was detected in the noncoding regions of both genes. However, synonymous variability was significantly higher for lbe: no nonsynonymous changes were observed in this gene. We argue that balancing selection impacts some synonymous sites of the lbe gene. Stability of mRNA secondary structure was significantly different between the lbe (but not lbl) haplotype groups and may represent a driving force of balancing selection in epistatically interacting synonymous sites. Balancing selection on synonymous sites may be the first, or one of a few such observations, in Drosophila. In contrast, recurrent positive selection on lbl at the protein level influenced evolution at three codon sites. Transcription factor binding-site profiles were different for lbe and lbl, suggesting that their developmental functions are not redundant. Combined with our previous results on nucleotide variation in esterase and other homeobox genes, these results suggest that interplay of balancing and directional selection may be a general feature of molecular evolution in Drosophila and other eukaryote genomes

Positive Selection within the Schizophrenia-Associated GABA(A) Receptor β(2) Gene

The gamma-aminobutyric acid type-A (GABA(A)) receptor plays a major role in inhibitory neurotransmissions. Intronic SNPs and haplotypes in GABRB2, the gene for GABA(A) receptor β(2) subunit, are associated with schizophrenia and correlated with the expression of two alternatively spliced β(2) isoforms. In the present study, using chimpanzee as an ancestral reference, high frequencies were observed for the derived (D) alleles of the four SNPs rs6556547, rs187269, rs1816071 and rs1816072 in GABRB2, suggesting the occurrence of positive selection for these derived alleles. Coalescence-based simulation showed that the population frequency spectra and the frequencies of H56, the haplotype having all four D alleles, significantly deviated from neutral-evolution expectation in various demographic models. Haplotypes containing the derived allele of rs1816072 displayed significantly less diversity compared to haplotypes containing its ancestral allele, further supporting positive selection. The variations in DD-genotype frequencies in five human populations provided a snapshot of the evolutionary history, which suggested that the positive selections of the D alleles are recent and likely ongoing. The divergence between the DD-genotype profiles of schizophrenic and control samples pointed to the schizophrenia-relevance of positive selections, with the schizophrenic samples showing weakened selections compared to the controls. These DD-genotypes were previously found to increase the expression of β(2), especially its long isoform. Electrophysiological analysis showed that this long β(2) isoform favored by the positive selections is more sensitive than the short isoform to the inhibition of GABA(A) receptor function by energy depletion. These findings represent the first demonstration of positive selection in a schizophrenia-associated gene

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family

Natural infection by the protozoan Leptomonas wallacei impacts the morphology, physiology, reproduction, and lifespan of the insect Oncopeltus fasciatus

Trypanosomatids are protozoan parasites that infect thousands of globally dispersed hosts, potentially affecting their physiology. Several species of trypanosomatids are commonly found in phytophagous insects. Leptomonas wallacei is a gut-restricted insect trypanosomatid only retrieved from Oncopeltus fasciatus. The insects get infected by coprophagy and transovum transmission of L. wallacei cysts. The main goal of the present study was to investigate the effects of a natural infection by L. wallacei on the hemipteran insect O. fasciatus, by comparing infected and uninfected individuals in a controlled environment. The L. wallacei-infected individuals showed reduced lifespan and morphological alterations. Also, we demonstrated a higher infection burden in females than in males. The infection caused by L. wallacei reduced host reproductive fitness by negatively impacting egg load, oviposition, and eclosion, and promoting an increase in egg reabsorption. Moreover, we associated the egg reabsorption observed in infected females, with a decrease in the intersex gene expression. Finally, we suggest alterations in population dynamics induced by L. wallacei infection using a mathematical model. Collectively, our findings demonstrated that L. wallacei infection negatively affected the physiology of O. fasciatus, which suggests that L. wallacei potentially has a vast ecological impact on host population growth

Mitogenomic phylogenetic analyses of the Delphinidae with an emphasis on the Globicephalinae

BACKGROUND: Previous DNA-based phylogenetic studies of the Delphinidae family suggest it has undergone rapid diversification, as characterised by unresolved and poorly supported taxonomic relationships (polytomies) for some of the species within this group. Using an increased amount of sequence data we test between alternative hypotheses of soft polytomies caused by rapid speciation, slow evolutionary rate and/or insufficient sequence data, and hard polytomies caused by simultaneous speciation within this family. Combining the mitogenome sequences of five new and 12 previously published species within the Delphinidae, we used Bayesian and maximum-likelihood methods to estimate the phylogeny from partitioned and unpartitioned mitogenome sequences. Further ad hoc tests were then conducted to estimate the support for alternative topologies. RESULTS: We found high support for all the relationships within our reconstructed phylogenies, and topologies were consistent between the Bayesian and maximum-likelihood trees inferred from partitioned and unpartitioned data. Resolved relationships included the placement of the killer whale (Orcinus orca) as sister taxon to the rest of the Globicephalinae subfamily, placement of the Risso's dolphin (Grampus griseus) within the Globicephalinae subfamily, removal of the white-beaked dolphin (Lagenorhynchus albirostris) from the Delphininae subfamily and the placement of the rough-toothed dolphin (Steno bredanensis) as sister taxon to the rest of the Delphininae subfamily rather than within the Globicephalinae subfamily. The additional testing of alternative topologies allowed us to reject all other putative relationships, with the exception that we were unable to reject the hypothesis that the relationship between L. albirostris and the Globicephalinae and Delphininae subfamilies was polytomic. CONCLUSION: Despite their rapid diversification, the increased sequence data yielded by mitogenomes enables the resolution of a strongly supported, bifurcating phylogeny, and a chronology of the divergences within the Delphinidae family. This highlights the benefits and potential application of large mitogenome datasets to resolve long-standing phylogenetic uncertainties

Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature

The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the “gold standard” of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK® Interbody Fusion System on a composite outcome of “clinical success” (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of “clinical success” (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial, with a high risk of bias, found no clinical relevant differences on pain and physical function when compared with circumferential spinal fusion at 2-year follow up. Because these are preliminary results, in addition to the high risk of bias, no conclusions can be drawn based on this study. In general, these results suggest that no clinical relevant differences between the total disc replacement and fusion techniques. The overall success rates in both treatment groups were small. Complications related to the surgical approach ranged from 2.1 to 18.7%, prosthesis related complications from 2.0 to 39.3%, treatment related complications from 1.9 to 62.0% and general complications from 1.0 to 14.0%. Reoperation at the index level was reported in 1.0 to 28.6% of the patients. In the three trials published, overall complication rates ranged from 7.3 to 29.1% in the TDR group and from 6.3 to 50.2% in the fusion group. The overall reoperation rate at index-level ranged from 3.7 to 11.4% in the TDR group and from 5.4 to 26.1% in the fusion group. In conclusion, there is low quality evidence that the Charité is non-inferior to the BAK cage at the 2-year follow up on the primary outcome measures. For the 5-year follow up, the same conclusion is supported only by very low quality evidence. For the ProDisc, there is very low quality evidence for contradictory results on the primary outcome measures when compared with anterior lumbar circumferential fusion. High quality randomized controlled trials with relevant control group and long-term follow-up is needed to evaluate the effectiveness and safety of TDR