Beyond overlap: Considering habitat preference and fitness outcomes in the umbrella species concept.

Umbrella species and other surrogate-species approaches to conservation provide an appealing framework to extend the reach of conservation efforts beyond single species. For the umbrella species concept to be effective, populations of multiple species of concern must persist in areas protected on behalf of the umbrella species. Most assessments of the concept, however, focus exclusively on geographic overlap among umbrella and background species, and not measures that affect population persistence (e.g., habitat quality or fitness). We quantified the congruence between the habitat preferences and nesting success of a high-profile umbrella species (greater sage-grouse, Centrocercus urophasianus, hereafter "sage-grouse"), and three sympatric species of declining songbirds (Brewer's sparrow Spizella breweri, sage thasher Oreoscoptes montanus, and vesper sparrow Pooecetes gramineus) in central Wyoming, USA during 2012 - 2013. We used machine-learning methods to create data-driven predictions of sage-grouse nest-site selection and nest survival probabilities by modeling field-collected sage-grouse data relative to habitat attributes. We then used field-collected songbird data to assess whether high-quality sites for songbirds aligned with those of sage-grouse. Nest sites selected by songbirds did not coincide with sage-grouse nesting preferences, with the exception that Brewer's sparrows preferred similar nest sites to sage-grouse in 2012. Moreover, the areas that produced higher rates of songbird nest survival were unrelated to those for sage-grouse. Our findings suggest that management actions at local scales that prioritize sage-grouse nesting habitat will not necessarily enhance the reproductive success of sagebrush-associated songbirds. Measures implemented to conserve sage-grouse and other purported umbrella species at broad spatial scales likely overlap the distribution of many species, however, broad-scale overlap may not translate to fine-scale conservation benefit beyond the umbrella species itself. The maintenance of microhabitat heterogeneity important for a diversity of species of concern will be critical for a more-holistic application of the umbrella species concept.

Recurrent Duplication and Diversification of Acrosomal Fertilization Proteins in Abalone.

Reproductive proteins mediating fertilization commonly exhibit rapid sequence diversification driven by positive selection. This pattern has been observed among nearly all taxonomic groups, including mammals, invertebrates, and plants, and is remarkable given the essential nature of the molecular interactions mediating fertilization. Gene duplication is another important mechanism that facilitates the generation of molecular novelty through functional divergence. Following duplication, paralogs may partition ancestral gene function (subfunctionalization) or acquire new roles (neofunctionalization). However, the contributions of duplication followed by sequence diversification to the molecular diversity of gamete recognition genes has been understudied in many models of fertilization. The marine gastropod mollusk abalone is a classic model for fertilization. Its two acrosomal proteins (lysin and sp18) are ancient gene duplicates with unique gamete recognition functions. Through detailed genomic and bioinformatic analyses we show how duplication events followed by sequence diversification has played an ongoing role in the evolution of abalone acrosomal proteins. The common ancestor of abalone had four members of its acrosomal protein family in a tandem gene array that repeatedly experienced positive selection. We find that both sp18 paralogs contain positively selected sites located in different regions of the paralogs, suggestive of functional divergence where selection acted upon distinct binding interfaces in each paralog. Further, a more recent species-specific duplication of both lysin and sp18 in the European abalone H. tuberculata is described. Despite clade-specific acrosomal protein paralogs, there are no concomitant duplications of egg coat proteins in H. tuberculata, indicating that duplication of egg proteins per se is not responsible for retention of duplicated acrosomal proteins. We hypothesize that, in a manner analogous to host/pathogen evolution, sperm proteins are selected for increased diversity through extensive sequence divergence and recurrent duplication driven by conflict mechanisms.

False individual patient data and zombie randomised controlled trials submitted to Anaesthesia.

Concerned that studies contain false data, I analysed the baseline summary data of randomised controlled trials when they were submitted to Anaesthesia from February 2017 to March 2020. I categorised trials with false data as 'zombie' if I thought that the trial was fatally flawed. I analysed 526 submitted trials: 73 (14%) had false data and 43 (8%) I categorised zombie. Individual patient data increased detection of false data and categorisation of trials as zombie compared with trials without individual patient data: 67/153 (44%) false vs. 6/373 (2%) false; and 40/153 (26%) zombie vs. 3/373 (1%) zombie, respectively. The analysis of individual patient data was independently associated with false data (odds ratio (95% credible interval) 47 (17-144); p = 1.3 × 10-12 ) and zombie trials (odds ratio (95% credible interval) 79 (19-384); p = 5.6 × 10-9 ). Authors from five countries submitted the majority of trials: China 96 (18%); South Korea 87 (17%); India 44 (8%); Japan 35 (7%); and Egypt 32 (6%). I identified trials with false data and in turn categorised trials zombie for: 27/56 (48%) and 20/56 (36%) Chinese trials; 7/22 (32%) and 1/22 (5%) South Korean trials; 8/13 (62%) and 6/13 (46%) Indian trials; 2/11 (18%) and 2/11 (18%) Japanese trials; and 9/10 (90%) and 7/10 (70%) Egyptian trials, respectively. The review of individual patient data of submitted randomised controlled trials revealed false data in 44%. I think journals should assume that all submitted papers are potentially flawed and editors should review individual patient data before publishing randomised controlled trials.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

Evidence for compromised data integrity in studies of liberal peri-operative inspired oxygen.

In 2016 the World Health Organization recommended intra-operative ventilation with 80% inspired oxygen to reduce surgical site infection rates, based upon a meta-analysis of 15 randomised controlled trials, of which two were by Mario Schietroma's research group. Five trials by this group have been retracted for duplication, plagiarism, statistical error and lack of ethical approval. We analysed 40 papers by this group: 24 randomised controlled trials (5064 participants) and 16 observational studies (1847 patients). There was evidence that data integrity was compromised in 38 out of the 40 analysed papers. The distribution of baseline characteristics in randomised controlled trials was unlikely, p = 1.5 × 10-8 : continuous variables within trials were heterogeneous, p = 1.9 × 10-9 , and categorical variables were homogeneous, p = 8.5 × 10-20 . Effects of interventions varied less than expected between studies: for categorical variables, for instance postoperative wound infection, p < 1 × 10-7 , and for continuous variables, for instance HLA-DR concentration, p = 0.00001. Of 184 calculable p values, for baseline variables or results, 179 (98%) were incorrect, ranging from three orders of magnitude too small to 10 orders of magnitude too large. Twenty-one graphs occurred 81 times in 23 out of 40 papers. Liberal peri-operative oxygen did not reduce surgical site infection in a meta-analysis of 20 trials that excluded seven trials by Mario Schietroma and colleagues (odds ratio (95%CI) 0.89 (0.73-1.08); p = 0.23). An update by the World Health Organization has now excluded trials of liberal oxygen by Schietroma's group, four of which have not been retracted. We conclude that Mario Schietroma's work should not inform practice until investigated.

Risk prediction models for major surgery: composing a new tune.

In this paper I explain why I think that most of the models that predict postoperative mortality should not be used when we're talking to patients about postoperative survival. Available models are isolated in time (from survival in the present) and space (from survival outside hospital). We know a lot about survival outside hospitals, with sufficient detail that we can discriminate between a man born in 1975 vs. 1976, or a woman aged 64 years vs. 65 years. We can use survival outside hospitals to inform what we do in hospital. I use my own survival to contrast with the survival of people older or younger than me. I will use my survival to illustrate how I might expect my mortality hazard to temporarily change when I have a scheduled operation (total hip replacement) and when I'm unwell and have an operation (for a fractured femoral neck). People live longer and longer and we operate on people older and older. We are also intervening earlier in progressive diseases, knowing that people are living long enough to experience harm from their progression. There is an evolving conflict between operating on older people and operating on younger people. Who has most to gain from the operation and who has most to gain from peri-operative critical care? Do we prioritise on reducing death now, in patients with relatively short life expectancies, or do we invest in the long-term survival of patients with relatively low rates of dying now? This conundrum is not informed by current risk models, with their focus on one to three postoperative months: we need to know survival outside hospital to gauge the value of what we do in hospital.

SECONDARY WALL ASSOCIATED MYB1 is a positive regulator of secondary cell wall thickening in Brachypodium distachyon and is not found in the Brassicaceae.

Grass biomass is comprised chiefly of secondary walls that surround fiber and xylem cells. A regulatory network of interacting transcription factors in part regulates cell wall thickening. We identified Brachypodium distachyon SECONDARY WALL ASSOCIATED MYB1 (SWAM1) as a potential regulator of secondary cell wall biosynthesis based on gene expression, phylogeny, and transgenic plant phenotypes. SWAM1 interacts with cellulose and lignin gene promoters with preferential binding to AC-rich sequence motifs commonly found in the promoters of cell wall-related genes. SWAM1 overexpression (SWAM-OE) lines had greater above-ground biomass with only a slight change in flowering time while SWAM1 dominant repressor (SWAM1-DR) plants were severely dwarfed with a striking reduction in lignin of sclerenchyma fibers and stem epidermal cell length. Cellulose, hemicellulose, and lignin genes were significantly down-regulated in SWAM1-DR plants and up-regulated in SWAM1-OE plants. There was no reduction in bioconversion yield in SWAM1-OE lines; however, it was significantly increased for SWAM1-DR samples. Phylogenetic and syntenic analyses strongly suggest that the SWAM1 clade was present in the last common ancestor between eudicots and grasses, but is not in the Brassicaceae. Collectively, these data suggest that SWAM1 is a transcriptional activator of secondary cell wall thickening and biomass accumulation in B. distachyon.

Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation.

The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative events and inform the perioperative management of patients undergoing surgery has increased over the last decade. CPET provides an objective assessment of exercise capacity preoperatively and identifies the causes of exercise limitation. This information may be used to assist clinicians and patients in decisions about the most appropriate surgical and non-surgical management during the perioperative period. Information gained from CPET can be used to estimate the likelihood of perioperative morbidity and mortality, to inform the processes of multidisciplinary collaborative decision making and consent, to triage patients for perioperative care (ward vs critical care), to direct preoperative interventions and optimization, to identify new comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide prehabilitation and rehabilitation, and to guide intraoperative anaesthetic practice. With the rapid uptake of CPET, standardization is key to ensure valid, reproducible results that can inform clinical decision making. Recently, an international Perioperative Exercise Testing and Training Society has been established (POETTS www.poetts.co.uk) promoting the highest standards of care for patients undergoing exercise testing, training, or both in the perioperative setting. These clinical cardiopulmonary exercise testing guidelines have been developed by consensus by the Perioperative Exercise Testing and Training Society after systematic literature review. The guidelines have been endorsed by the Association of Respiratory Technology and Physiology (ARTP).

Data fabrication and other reasons for non-random sampling in 5087 randomised, controlled trials in anaesthetic and general medical journals.

Randomised, controlled trials have been retracted after publication because of data fabrication and inadequate ethical approval. Fabricated data have included baseline variables, for instance, age, height or weight. Statistical tests can determine the probability of the distribution of means, given their standard deviation and the number of participants in each group. Randomised, controlled trials have been retracted after the data distributions have been calculated as improbable. Most retracted trials have been written by anaesthetists and published by specialist anaesthetic journals. I wanted to explore whether the distribution of baseline data in trials was consistent with the expected distribution. I wanted to determine whether trials retracted after publication had distributions different to trials that have not been retracted. I wanted to determine whether data distributions in trials published in specialist anaesthetic journals have been different to distributions in non-specialist medical journals. I analysed the distribution of 72,261 means of 29,789 variables in 5087 randomised, controlled trials published in eight journals between January 2000 and December 2015: Anaesthesia (399); Anesthesia and Analgesia (1288); Anesthesiology (541); British Journal of Anaesthesia (618); Canadian Journal of Anesthesia (384); European Journal of Anaesthesiology (404); Journal of the American Medical Association (518) and New England Journal of Medicine (935). I chose these journals as I had electronic access to the full text. Trial p values were distorted by an excess of baseline means that were similar and an excess that were dissimilar: 763/5015 (15.2%) trials that had not been retracted from publication had p values that were within 0.05 of 0 or 1 (expected 10%), that is, a 5.2% excess, p = 1.2 × 10-7 . The p values of 31/72 (43%) trials that had been retracted after publication were within 0.05 of 0 or 1, a rate different to that for unretracted trials, p = 1.03 × 10-10 . The difference between the distributions of these two subgroups was confirmed by comparison of their overall distributions, p = 5.3 × 10-15 . Each journal exhibited the same abnormal distribution of baseline means. There was no difference in distributions of baseline means for 1453 trials in non-anaesthetic journals and 3634 trials in anaesthetic journals, p = 0.30. The rate of retractions from JAMA and NEJM, 6/1453 or 1 in 242, was one-quarter the rate from the six anaesthetic journals, 66/3634 or 1 in 55, relative risk (99%CI) 0.23 (0.08-0.68), p = 0.00022. A probability threshold of 1 in 10,000 identified 8/72 (11%) retracted trials (7 by Fujii et al.) and 82/5015 (1.6%) unretracted trials. Some p values were so extreme that the baseline data could not be correct: for instance, for 43/5015 unretracted trials the probability was less than 1 in 1015 (equivalent to one drop of water in 20,000 Olympic-sized swimming pools). A probability threshold of 1 in 100 for two or more trials by the same author identified three authors of retracted trials (Boldt, Fujii and Reuben) and 21 first or corresponding authors of 65 unretracted trials. Fraud, unintentional error, correlation, stratified allocation and poor methodology might have contributed to the excess of randomised, controlled trials with similar or dissimilar means, a pattern that was common to all the surveyed journals. It is likely that this work will lead to the identification, correction and retraction of hitherto unretracted randomised, controlled trials.

Bias in beliefs about the self is associated with depressive but not anxious mood.

BACKGROUND: Biases in beliefs about the self are associated with psychopathology and depressive and anxious mood, but it is not clear if both negative and positive beliefs are associated with depression or anxiety. We examined these relationships in people who present with a wide range of depressive and anxious mood across diagnostic categories. METHODS: We probed positive and negative beliefs about the self with a task in which 74 female participants with either affective disorder (depression and/or anxiety), borderline personality disorder or no psychiatric history indicated the degree to which 60 self-related words was "like them" or "not like them". Depressive and anxious mood were assessed with the Beck Depression Inventory-II and the Beck Anxiety Inventory. RESULTS: The participants with no psychiatric history (n=25) reported a positive bias in their beliefs about the self, the participants with affective disorder (n=23) reported no bias, and the participants with BPD (n=26) reported a negative bias. Two hierarchical multiple regressions demonstrated that the positive and negative beliefs contributed additively to the ratings of depression (corrected for anxiety), but did not contribute to the ratings of anxiety (corrected for depression). LIMITATIONS: Despite the apparent small sample size, the regression analyses indicated adequate sampling. Anxiety is a much more heterogeneous condition than is depression, so it may be difficult to find relevant self-descriptors. Only measures of endorsement were used. CONCLUSIONS: Biases in beliefs about the self are associated with depressed, but not anxious mood, across diagnostic categories.

Using predicted 30 day mortality to plan postoperative colorectal surgery care: a cohort study.

BACKGROUND: Preoperative identification of high-risk surgical patients might help to reduce postoperative morbidity and mortality. Using a patient's predicted 30 day mortality to plan postoperative high-dependency unit (HDU) care after elective colorectal surgery might be associated with reduced postoperative morbidity. METHODS: The 30 day postoperative mortality was predicted for 504 elective colorectal surgical patients in a preoperative clinic. The prediction was used to determine postoperative surgical ward or HDU care. Those with a predicted 30 day mortality of 1-3% mortality, and thus deemed at intermediate risk, had either planned HDU care (n=68) or planned ward care (n=139). The main outcome measures were emergency laparotomy and unplanned critical care admission. RESULTS: There were more emergency laparotomies and unplanned critical care admissions in patients with a predicted 30 day mortality of 1-3% who went to an HDU after surgery compared with patients who went to a ward: 0 vs 14 (10%), P=0.0056 and 0 vs 22 (16%), P=0.0002, respectively. CONCLUSIONS: Planned postoperative critical care was associated with a lower rate of complications after elective colorectal surgery.