bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes and predictors of skin sodium concentration in dialysis patients
Authors: Salerno Fabio R , Akbari Alireza , Lemoine Sandrine , Filler Guido , Scholl Timothy J , McIntyre Christopher W
Published: January 2022

Background

Sodium-23 magnetic resonance imaging (23Na MRI) allows the measurement of skin sodium concentration ([Na+]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition.

Methods

This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na+] quantification with leg 23Na MRI at the study’s beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan–Meier survival function after stratification into skin [Na+] quartiles. Cox proportional hazards regression was used to model the association between skin [Na+] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na+].

Results

A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353–602). Increasing skin [Na+] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ2(1) = 3.926, log-rank χ2(1) = 5.685; P for trend <0.05 in both instances). Skin [Na+] was associated with all-cause mortality {hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988–8.101]; P < 0.001} and composite events [HR 2.332 (95% CI 1.378–3.945); P < 0.01], independently of age, sex, serum [Na+] and albumin. In multiple regression models, dialysate [Na+], serum albumin and congestive heart failure were significantly associated with skin [Na+] in HD patients (R2adj = 0.62).

Conclusions

Higher skin [Na+] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.
Hyperlactataemia and acid–base disturbances in normotensive patients with acute heart failure
Authors: Bar Omer , Aronson Doron
Published: January 2022

Aims

Acute heart failure (AHF) may be associated with low-tissue perfusion and/or hypoxaemia leading to increased lactate levels and acid–base perturbations. Few data are available on the clinical significance of elevated lactate levels and primary acid–base disorders in the setting of AHF.

Methods and results

Arterial blood gas was obtained at admission in 4012 normotensive (systolic blood pressure ≥ 90 mmHg) patients with AHF. The association between lactate levels and acid–base status and in-hospital mortality was determined using multivariable logistic regression. Hyperlactataemia (>2 mmol/L) was present in 38.0% of patients and was strongly associated with markers of sympathetic activation, such as hyperglycaemia. Hyperlactataemia was present in 31.0%, 43.7%, and 42.0% of patients with normal pH, acidosis, and alkalosis, respectively. In-hospital mortality occurred in 16.4% and 11.1% of patients with and without hyperlactataemia [adjusted odds ratio (OR) 1.49; 95% confidence interval (CI) 1.22–1.82, P < 0.0001]. Compared with normal pH, the OR for in-hospital mortality was 2.48 (95% CI 1.95–3.16, P < 0.0001) in patients with acidosis and 1.77 (95% CI 1.32–2.26, P < 0.0001) in patients with alkalosis. The risk for in-hospital mortality was high with acidosis (18.1%) or alkalosis (10.4%) even with normal lactate. The most common primary acid–base disturbances included metabolic acidosis, respiratory acidosis, and metabolic alkalosis with respiratory acidosis having the highest risk for in-hospital mortality.

Conclusion

Hyperlactataemia was common in patients without hypotension and was associated with increased risk for in-hospital mortality. Hyperlactataemia is not associated with any specific acid–base disorder. Acute heart failure patients also present with diverse acid–base disorders portending increased in-hospital mortality.
Survey Research Among Older Migrants: Age-Related Differences in Contact and Cooperation
Authors: Seibel Verena , Haan Marieke
Published: January 2022

Background and Objectives

Given the increasing academic interest in older migrants, this study aims at examining the likelihood of establishing contact and cooperation in a survey among first-generation migrants in Germany, comparing migrants of age 50 and older with younger migrants (aged 16–49).

Research Design and Methods

We analyze data from the Migrants’ Welfare State Attitudes (MIFARE) study collected in Germany, which contains information about first-generation migrants from 9 different origin groups living in private households. Potential survey participants were contacted via mail and invited to participate in a paper- or online-based survey. In addition, an incentive experiment was implemented and age-dependent response rates were analyzed. Using logistic regression analyses, we compare older and younger migrants with regard to their likelihood of contact, cooperation, reaction to incentives, and mode choice.

Results

Within the MIFARE study, older migrants are more likely to be contacted than younger ones. Older migrants are also more likely to cooperate in survey research than younger migrants. Both groups respond equally positively to the use of unconditional incentives. Lastly, older migrants show a strong preference to fill out the questionnaire on paper, rather than online.

Discussion and Implications

Older first-generation migrants living in private households are easier to contact and are more likely to cooperate in survey research than younger first-generation migrants. Offering unconditional incentives and surveys on paper are likely to increase response rates among older migrants.
Aerial detection of beached marine plastic using a novel, hyperspectral short-wave infrared (SWIR) camera
Authors: Cocking Jennifer , Narayanaswamy Bhavani E , Waluda Claire M , Williamson Benjamin J
Published: January 2022

Plastic pollution in the marine environment is a pervasive, global problem that threatens wildlife and human health. Routine monitoring is required to determine pollution hotspots, focus clean-up efforts, and assess the efficacy of legislation implemented to reduce environmental contamination. The shoreline represents an accessible area, relative to open water, from which to monitor this. Unmanned aerial vehicles (UAVs) offer a low-cost platform for remote sensing that operates below cloud coverage, which can interfere with satellite imagery. Detection of plastic using visible light is limited however, and results may be improved by using short-wave infrared (SWIR) imagery to collect chemical information. Within the commercial recycling industry, plastic items are sorted successfully based on their composition using SWIR instrumentation that measures the chemical spectra of waste items under controlled illumination. Here, proof of concept is established for aerial detection of domestic and shoreline-harvested plastic items on a beach under natural sunlight with a lightweight (800 g), hyperspectral SWIR camera deployed at an altitude of ∼ 5 m over ∼ 30-m transects. The results of spectral correlation mapping to compare imagery spectra to polyethylene and polypropylene reference spectra demonstrate that these two polymers can be successfully detected with this novel method.
Calanus finmarchicus basin scale life history traits and role in community carbon turnover during spring
Authors: Jónasdóttir Sigrún H , Naustvoll Lars , Teglhus Frederik Wolff , Agersted Mette Dalgaard , Grenwald Julie C , Melle Webjørn , Nielsen Torkel Gissel
Published: January 2022

The copepod Calanus finmarchicus was investigated in four Subpolar Basins, Labrador, Irminger, Iceland, and Norwegian Seas, during spring, covering the time of ascent, grazing, and initiation of reproduction in the area. Lipid content, spawning activity, and stage composition and vital rates, such as egg and faecal pellet production were measured and linked to environmental parameters. Specific egg- and faecal pellet production rates varied with diatom biomass and were negatively correlated with temperature. Comparison of the various biological indicators revealed different life history traits C. finmarchicus has adopted in the different basins. In Labrador Sea, the females have invested in large eggs compared to the remaining basins. Labrador and Irminger Sea C. finmarchicus invest in size that we propose to be adaptation to cope with warmer overwintering habitats resulting in larger potential lipid storage capacity, while the Iceland and Norwegian Sea females can invest their remaining lipid storage in spring to fuel lipid-driven egg production. Grazing pressure on the phytoplankton community was estimated and compared between copepod and two dominating groups of protozooplankton; ciliates and heterotrophic dinoflagellates. Despite approximately the same biomass in the upper 100 m, the grazing impact of the protozoan grazers was an order of magnitude higher than the C. finmarchicus dominated mesozooplankton. This illustrates the importance to also include the smallest grazers when studying the spring bloom in high latitude marine ecosystems if the fate of the primary production should be fully understood.
Being able is not necessarily being willing: governance implications of social, policy, and science-related factors influencing uptake of selective gear
Authors: Steins Nathalie A , Mattens Alessa L , Kraan Marloes
Published: January 2022

Improving the selectivity of fishing gear and practices has been a challenge for fishers, scientists, and policy-makers for decades. In Europe, urgency increased with the introduction of the landing obligation. Voluntary uptake of proven selective gears has been poor across the globe. To increase uptake levels, a move from science-led to industry-led development of selective gears has been advocated. In the Netherlands, gear innovation has, since the mid-2000s, been fisher-led. Nevertheless, this did not result in the assumed increase in uptake. Our qualitative study amongst Dutch demersal fishers shows that decisions to voluntarily adopt proven fishing gear are driven by a complex interplay of social, policy, and science-related factors. These can be attributed to two behavioural components: Willingness and Ability. Willingness, our study showed, is closely linked to: (i) intrinsic motivations and beliefs about sustainable fishing as well as perceptions about the motivations and behaviour of other fishers; (ii) the extent to which fishers consider policy goals and regulations as legitimate; and (iii) strong normative beliefs amongst fishers about the presence (or absence) of a level playing field, in terms of both the same rules applying to all and trust in compliance and enforcement. Ability is associated with knowledge, skills, economic, and legal possibilities to enable voluntary uptake, and tends to be the focus of science and policy. We conclude that a narrow focus on Ability as a driver for encouraging selective fishing is unlikely to result in real changes, and recommend a stronger emphasis on addressing social, policy- and science-related factors associated with Willingness in encouraging more selective fisheries.
Splitting schemes for a Lagrange multiplier formulation of FSI with immersed thin-walled structure: stability and convergence analysis
Authors: Annese Michele , Fernández Miguel A , Gastaldi Lucia
Published: January 2022

The numerical approximation of incompressible fluid–structure interaction problems with Lagrange multiplier is generally based on strongly coupled schemes. This delivers unconditional stability, but at the expense of solving a computationally demanding coupled system at each time step. For the case of the coupling with immersed thin-walled solids, we introduce a class of semi-implicit coupling schemes that avoids strongly coupling without compromising stability and accuracy. A priori energy and error estimates are derived. The theoretical results are illustrated through numerical experiments in an academic benchmark.
Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer
Authors: Rossetti Rafaela , Brand Heloísa , Lima Sarah Caroline Gomes , Furtado Izadora Peter , Silveira Roberta Maraninchi , Fantacini Daianne Maciely Carvalho , Covas Dimas Tadeu , de Souza Lucas Eduardo Botelho
Published: January 2022

Immune checkpoint (IC) blockade using monoclonal antibodies is currently one of the most successful immunotherapeutic interventions to treat cancer. By reinvigorating antitumor exhausted T cells, this approach can lead to durable clinical responses. However, the majority of patients either do not respond or present a short-lived response to IC blockade, in part due to a scarcity of tumor-specific T cells within the tumor microenvironment. Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CARs) or engineered T-cell receptors (TCRs) provide the necessary tumor-specific immune cell population to target cancer cells. However, this therapy has been considerably ineffective against solid tumors in part due to IC-mediated immunosuppressive effects within the tumor microenvironment. These limitations could be overcome by associating adoptive cell transfer of genetically engineered T cells and IC blockade. In this comprehensive review, we highlight the strategies and outcomes of preclinical and clinical attempts to disrupt IC signaling in adoptive T-cell transfer against cancer. These strategies include combined administration of genetically engineered T cells and IC inhibitors, engineered T cells with intrinsic modifications to disrupt IC signaling, and the design of CARs against IC molecules. The current landscape indicates that the synergy of the fast-paced refinements of gene-editing technologies and synthetic biology and the increased comprehension of IC signaling will certainly translate into a novel and more effective immunotherapeutic approaches to treat patients with cancer.
Transcriptome analyses indicate that heat stress-induced inflammation in white adipose tissue and oxidative stress in skeletal muscle is partially moderated by zilpaterol supplementation in beef cattle
Authors: Reith Rachel R , Sieck Renae L , Grijalva Pablo C , Swanson Rebecca M , Fuller Anna M , Diaz Duarte E , Schmidt Ty B , Yates Dustin T , Petersen Jessica L
Published: January 2022

Heat stress (HS) triggers oxidative stress, systemic inflammation, and disrupts growth efficiency of livestock. β-adrenergic agonists supplemented to ruminant livestock improve growth performance, increase skeletal muscle mass, and decrease carcass fat. The objective of this study was to understand the independent and interacting effects of HS and zilpaterol hydrochloride (ZH) supplementation on the transcriptome of subcutaneous white adipose tissue and the longissimus dorsi muscle in steers. Twenty-four Red Angus-based steers were assigned to thermoneutral (TN; Temperature Humidity Index [THI] = 68) or HS (THI = 73–85) conditions and were not supplemented or supplemented with ZH (8.33 mg/kg/d) for 21 d in a 2 × 2 factorial. Steers in the TN condition were pair-fed to the average daily feed intake of HS steers. RNA was isolated from adipose tissue and skeletal muscle samples collected via biopsy on 3, 10, and 21 d and sequenced using 3ʹ Tag-Seq to an achieved average depth of 3.6 million reads/sample. Transcripts, mapped to ARS-UCD1.2, were quantified. Differential expression (DE) analyses were performed in DESeq2 with a significance threshold for false discovery rate of 0.05. In adipose, 4 loci (MISP3, APOL6, SLC25A4, and S100A12) were DE due to ZH on day 3, and 2 (RRAD, ALB) were DE due to the interaction of HS and ZH on day 10 (Padj < 0.05). In muscle, 40 loci (including TENM4 and OAZ1) were DE due to ZH on day 10, and 6 loci (HIF1A, LOC101903734, PDZD9, HNRNPU, MTUS1, and TMCO6) were DE due to environment on day 21 (Padj < 0.05). To explore biological pathways altered by environment, supplement, and their interaction, loci with DE (Praw < 0.05) were evaluated in Ingenuity Pathway Analysis. In adipose, 509 pathways were predicted to be altered (P < 0.01): 202 due to HS, 126 due to ZH, and 181 due to the interaction; these included inflammatory pathways predicted to be upregulated due to HS but downregulated due to the interaction of HS and ZH. In muscle, 113 pathways were predicted to be altered (P < 0.01): 23 due to HS, 66 due to ZH, and 24 due to the interaction of HS and ZH. Loci and pathway data in muscle suggest HS induced oxidative stress and that the stress response was moderated by ZH. Metabolic pathways were predicted to be altered due to HS, ZH, and their interaction in both tissues. These data provide evidence that HS and ZH interact to alter expression of genes in metabolic and immune function pathways and that ZH moderates some adverse effects of HS.
A leaderless mRNA including tRNA-like sequence encodes a small peptide that regulates the expression of GcvB small RNA inEscherichia coli
Authors: Muto Akira , Goto Simon , Kurita Daisuke , Ushida Chisato , Soma Akiko , Himeno Hyota
Published: January 2022

A tRNA-like sequence conserved in the genomes of all Escherichia coli strains was found. The sequence resembles arginine-tRNA, which is present in E. coli pathogenic islands and phages. Expression experiments revealed that this sequence is a part of a leaderless mRNA encoding a short peptide (60 amino acids: XtpA). A deletion mutant of this gene is more sensitive than wild-type cell to several aminoglycoside antibiotics at low concentrations. Further analyses indicated that XtpA positively regulates the expression of GcvB small RNA, which is involved in the intrinsic resistance to aminoblycosides in E. coli.
Pruritus in the Pediatric Burn Population
Authors: Zuccaro Jennifer , Budd Diandra , Kelly Charis , Fish Joel S
Published: January 2022

Postburn pruritus is a significant issue that can have a devastating impact on patient quality of life. Despite its known negative impact, few studies have focused on the pediatric population. Thus, the aim of this study was to determine the incidence of pruritus among pediatric burn patients as well as identify its predictive factors and commonly used treatments, including the novel use of laser therapy. A retrospective analysis of all burn patients treated at our pediatric burn center from 2009 to 2017 was conducted. The primary outcome measure was the presence or absence of pruritus at any point following the burn. One thousand seven hundred and eighty-three patients met the inclusion criteria for this study. The mean age at injury was 3.67 years (SD = 4.02) and the mean burn TBSA was 3.48% (SD = 4.81) with most burns resulting from scalds (66%). In total, 665 patients (37.3%) experienced pruritus. Following multivariable logistic regression, TBSA, age >5 years, burns secondary to fire/flame, and burn depth, were identified as significant predictors of pruritus (P < .05). Pruritus was treated with diphenhydramine (85.0%), hydroxyzine (37.3%), and gabapentin (4.2%) as well as massage (45.7%), pressure garments (20.0%), and laser therapy (8.6%). This study addresses the knowledge gap in the literature related to postburn pruritus among pediatric patients and includes one of the largest patient cohorts published to date. Moreover, the results further contribute to our understanding of postburn pruritus in children and may help us to predict which patients are most likely to be affected, so that treatment can be initiated as soon as possible.
Cost-Effectiveness of Tight Control for Crohn’s Disease With Adalimumab-Based Treatment: Economic Evaluation of the CALM Trial From a Canadian Perspective
Authors: Lakatos Peter L , Kaplan Gilaad G , Bressler Brian , Khanna Reena , Targownik Laura , Jones Jennifer , Rahal Yasmine , McHugh Kevin , Panaccione Remo
Published: January 2022

Crohn’s disease (CD) is associated with reduced quality of life, increased absenteeism and high direct medical costs resulting from frequent hospitalizations and surgeries. Tumor necrosis factor–alpha inhibitors (TNFi’s) have transformed the therapeutic landscape and enabled a shift from a symptom control to a treat-to-target strategy. The Effect of Tight Control Management on Crohn’s Disease (CALM) trial demonstrated tight control (TC), with TNFi dose changes informed by biochemical markers of inflammation, achieved higher mucosal healing rates compared with conventional management (CM) based on symptoms. A Markov model compared TC and CM strategies from the perspective of the Canadian public payer using patient-observation data from the CALM trial. A regression model estimated weekly CD Activity Index–based transition matrices over a 5-year horizon and included covariates to improve extrapolation of outcomes beyond the 48-week trial assessment period. Costs of CD-related hospitalizations, biomarker tests and adalimumab injections were sourced from public data. Other direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Absenteeism was monetized and included in a sensitivity analysis. Over the 5-year time horizon, TC reduced hospitalization costs by 64% compared with CM. Other direct medical costs were reduced by 22%; adalimumab costs increased by 38%, generating an ICER of $35,168 per QALY gained. Absenteeism costs were reduced by 54%, and, when that was included in the model, TC became dominant compared with CM. Management of CD with TC is cost-effective compared with CM in Canada and is dominant if indirect costs associated with absenteeism are included. Trial registration number: NCT01235689.
Covert Qualitative Research as a Method to Study Human Rights Under Authoritarian Regimes
Authors: Hopman Marieke J
Published: January 2022

This article considers whether covert research methods may be an ethically acceptable method for doing human rights research in areas under control of authoritarian regimes, and, if so, how this research can and should be conducted. The author’s study on the rights of children living in Western Sahara under Moroccan control, where a covert qualitative research method was employed, is taken as a central case study. The article concludes that covert qualitative research in authoritarian zones is ethically acceptable, and sometimes even necessary, under three conditions: 1) the research aims to contribute to the protection of human rights; 2) research subjects remain anonymous; 3) there is no other, overt way to obtain the necessary data. The article aims to present a challenging yet sometimes necessary and valuable method for studying human rights in areas that otherwise may be inaccessible to human rights researchers. It contributes to a longer standing debate on the ethical acceptability of covert research methods, as well as to provide practical guidance to researchers (both academic and non-academic) who are considering using this method to study human rights violations.
Overseas immigration liaison officers: ‘Knowledge brokers’ and transnational spaces of mid-level negotiations shaping extraterritorial migration control practices
Authors: Ostrand Nicole
Published: January 2022

A significant yet overlooked aspect in many states’ extraterritorial migration control efforts is their immigration liaison officers (ILOs) posted to foreign jurisdictions, who make decisions and take actions abroad to support their country’s immigration goals. Importantly, this occurs within an interconnected system of nation-states, requiring mid-level officials from multiple states to co-operate. Yet, there is very little analysis on what happens in these foreign jurisdictions where officials from across national and organisational boundaries interact and negotiate the management of migration flows. This article aims to fill this gap by drawing on empirical research on the UK’s overseas immigration liaison network. Analysis is based on original interviews with Home Office officials, Freedom of Information requests, and documentary research. I find that UK ILOs are a main contact point between the country they represent, local authorities in the host state, and Global North counterparts from other states, making them key sites for the transnational exchange of information, ‘intelligence’ and ‘know-how’. In this way, they are like ‘knowledge brokers’, contributing to a ‘global–local diffusion’ of ideas. Despite power hierarchies, this is not a one-way transfer from the Global North to the South. Instead, I find Global South actors are also key subjects in this process. By going beyond policies on paper and formal inter-state agreements, this study offers important insight into a largely hidden yet central part of a state’s extraterritorial migration control: informal spaces of negotiation between mid-level officials from across national and organisational boundaries who negotiate and contest migration control practices.
Plastics-to-syngas photocatalysed by Co–Ga2O3 nanosheets
Authors: Xu Jiaqi , Jiao Xingchen , Zheng Kai , Shao Weiwei , Zhu Shan , Li Xiaodong , Zhu Junfa , Pan Yang , Sun Yongfu , Xie Yi
Published: January 2022

Plastics take hundreds of years to degrade naturally, while their chemical degradation typically requires high temperature and pressure. Here, we first utilize solar energy to realize the sustainable and efficient plastic-to-syngas conversion with the aid of water at ambient conditions. As an example, the commercial plastic bags could be efficiently photoconverted into renewable syngas by Co–Ga2O3 nanosheets, with hydrogen and carbon monoxide formation rates of 647.8 and 158.3 μmol g−1 h−1. In situ characterizations and labelling experiments unveil water is photoreduced into hydrogen, while non-recyclable plastics including polyethylene bags, polypropylene boxes and polyethylene terephthalate bottles are photodegraded into carbon dioxide, which is further selectively photoreduced into carbon monoxide. In-depth investigation illustrates that the efficiency of syngas production mainly depends on the carbon dioxide reduction process and hence photocatalysts of high carbon dioxide reduction activity should be designed to promote the efficiency of plastic-to-syngas conversion in the future. The concept for the photoreforming of non-recyclable plastics into renewable syngas helps to eradicate ‘white pollution’ and alleviate the energy crisis simultaneously.
Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma
Authors: Jun Tomi , Hahn Noah M , Sonpavde Guru , Albany Constantine , MacVicar Gary R , Hauke Ralph , Fleming Mark , Gourdin Theodore , Jana Bagi , Oh William K , Taik Patricia , Wang Huan , Varadarajan Ajay Ramakrishnan , Uzilov Andrew , Galsky Matthew D
Published: January 2022

Background

Treatment options have been historically limited for cisplatin-ineligible patients with advanced urothelial carcinoma (UC). Given the need for alternatives to platinum-based chemotherapy, including non-chemotherapy regimens for patients with both impaired renal function and borderline functional status, in 2010 (prior to the immune checkpoint blockade era in metastatic UC), we initiated a phase II trial to test the activity of everolimus or everolimus plus paclitaxel in the cisplatin-ineligible setting.

Methods

This was an open-label phase II trial conducted within the US-based Hoosier Cancer Research Network (ClinicalTrials.gov number: NCT01215136). Patients who were cisplatin-ineligible with previously untreated advanced UC were enrolled. Patients with both impaired renal function and poor performance status were enrolled into cohort 1; patients with either were enrolled into cohort 2. Patients received everolimus 10 mg daily alone (cohort 1) or with paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle (cohort 2). The primary outcome was clinical benefit at 4 months. Secondary outcomes were adverse events, progression-free survival (PFS), and 1-year overall survival (OS). Exploratory endpoints included genomic correlates of outcomes. The trial was not designed for comparison between cohorts.

Results

A total of 36 patients were enrolled from 2010 to 2018 (cohort 1, N = 7; cohort 2, N = 29); the trial was terminated due to slow accrual. Clinical benefit at 4 months was attained by 0 (0%, 95% confidence interval [CI] 0-41.0%) patients in cohort 1 and 11 patients (37.9%, 95% CI 20.7-57.7%) in cohort 2. Median PFS was 2.33 (95% CI 1.81-Inf) months in cohort 1 and 5.85 (95% CI 2.99-8.61) months in cohort 2. Treatment was discontinued due to adverse events for 2 patients (29%) in cohort 1 and 11 patients (38%) in cohort 2. Molecular alterations in microtubule associated genes may be associated with treatment benefit but this requires further testing.

Conclusion

Everolimus plus paclitaxel demonstrates clinical activity in cisplatin-ineligible patients with metastatic UC, although the specific contribution of everolimus cannot be delineated. Patients with both impaired renal function and borderline functional status may be difficult to enroll to prospective trials. (ClinicalTrials.gov Identifier NCT01215136).
The Welfare Effects of Transportation Infrastructure Improvements
Authors: Allen Treb , Arkolakis Costas
Published: January 2022

Each year in the US, hundreds of billions of dollars are spent on transportation infrastructure and billions of hours are lost in traffic. We develop a quantitative general equilibrium spatial framework featuring endogenous transportation costs and traffic congestion and apply it to evaluate the welfare impact of transportation infrastructure improvements. Our approach yields analytical expressions for transportation costs between any two locations, the traffic along each link of the transportation network, and the equilibrium distribution of economic activity across the economy, each as a function of the underlying quality of infrastructure and the strength of traffic congestion. We characterize the properties of such an equilibrium and show how the framework can be combined with traffic data to evaluate the impact of improving any segment of the infrastructure network. Applying our framework to both the US highway network and the Seattle road network, we find highly variable returns to investment across different links in the respective transportation networks, highlighting the importance of well-targeted infrastructure investment.
Credit Ratings and Market Information
Authors: Piccolo Alessio , Shapiro Joel
Published: January 2022

Accurate credit ratings are important for both investors and regulators. We demonstrate that the market for credit risk provides an important source of discipline for credit rating agencies (CRAs). We examine a model in which a CRA’s rating is followed by a market for credit risk that provides a public signal – the price. More informative trading increases the CRA’s incentives to be accurate by making rating errors more transparent. We show that this source of discipline is (a) robust to moral hazard, multiple CRAs, and connected primary and secondary markets and (b) specific to the market for credit risk.
Relating Glutamate, Conditioned, and Clinical Hallucinations via 1H-MR Spectroscopy
Authors: Leptourgos Pantelis , Bansal Sonia , Dutterer Jenna , Culbreth Adam , Powers Albert , Suthaharan Praveen , Kenney Joshua , Erickson Molly , Waltz James , Wijtenburg S Andrea , Gaston Frank , Rowland Laura M , Gold James , Corlett Philip
Published: January 2022

Background and Hypothesis

Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs.

Study Design

Here we induce hallucinated tones by associating tones with the presentation of a visual cue. We find that people with schizophrenia who hear voices are more prone to the effect and using computational modeling we show they overweight their prior beliefs. In the same participants, we also measured glutamate levels in anterior insula, anterior cingulate, dorsolateral prefrontal, and auditory cortices, using magnetic resonance spectroscopy.

Study Results

We found a negative relationship between prior-overweighting and glutamate levels in the insula that was not present for any of the other voxels or parameters.

Conclusions

Through computational psychiatry, we bridge a pathophysiological theory of psychosis (glutamate hypofunction) with a cognitive model of hallucinations (prior-overweighting) with implications for the development of new treatments for hallucinations.
Unsuppressed Striatal Activity and Genetic Risk for Schizophrenia Associated With Individual Cognitive Performance Under Social Competition
Authors: Zhang Yuyanan , Li Mingzhu , Zhang Xiao , Zhang Dai , Tan Hao-Yang , Yue Weihua , Yan Hao
Published: January 2022

Background and Hypothesis

Social competition affects human behaviors by inducing psychosocial stress. The neural and genetic mechanisms of individual differences of cognitive-behavioral response to stressful situations in a competitive context remain unknown. We hypothesized that variation in stress-related brain activation and genetic heterogeneity associated with psychiatric disorders may play roles towards individually differential responses under stress.

Study Design

A total of 419 healthy subjects and 66 patients with schizophrenia were examined functional magnetic resonance imaging during working memory task including social competition stressors. We explored the correlation between stress-induced brain activity and individual working memory performance. The partial least squares regression was performed to examine the genetic correlates between stress-related activity and gene expression data from Allen Human Brain Atlas. Polygenic risk score (PRS) was used to assess individual genetic risk for schizophrenia.

Study Results

Greater suppression of bilateral striatal activity was associated with better behavioral improvement in working memory manipulation under social competition (left: rPearson = −0.245, P = 4.0 × 10−6, right: rPearson = −0.234, P = 1.0 × 10−5). Genes transcriptionally related to stress-induced activation were linked to genetic risk for schizophrenia (PFDR < 0.005). Participants with decreased accuracy under social competition exhibited higher PRS of schizophrenia (t = 2.328, P = .021). Patients with schizophrenia showed less suppressed striatal activity under social stress (F = 13.493, P = 3.5 × 10−4).

Conclusions

Striatal activity change and genetic risk for schizophrenia might play a role in the individually behavioral difference in working memory manipulation under stress.
Doctoring the Script: Crime Writing, Order and Medical Authority in the Oeuvre of Dr Augustin Cabanès, 1894–1928
Authors: Powell Julie M
Published: January 2022

In 1894, Augustin Cabanès founded La Chronique médicale, a one-of-a-kind medical journal that allowed the doctor to indulge his interest in the practise of médecin historique. Historical medicine used modern forensic knowledge to ‘solve’ the mysterious deaths of history. Such retrospective diagnoses were communicated to readers in a familiar literary style, that of crime writing. Developed at the intersection of medical professionalisation and specialisation, the rise of forensic medicine, and the popularisation of crime writing, Cabanès’s work promoted a clear viewpoint on the role of the medical man in fin-de-siècle French society. Through the practise of historical medicine and the medium of crime writing, Cabanès aimed to bolster faith in forensic medicine, to promote the doctor as moral authority, and, relatedly, to establish scientific, and especially medical, practise as critical to the maintenance of the social order during volatile periods of social dislocation and war.
Sepsis and the microcirculation: the impact on outcomes
Authors: Yajnik Vishal , Maarouf Rami
Published: January 2022

Purpose of review

Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of sepsis and septic shock have shifted to focus on the diversity of causes of dysregulated host-response we have seen an emerging phenotype where tissue hypoxia persists despite adequate macrocirculatory parameters. Interest in the topic of microcirculation is re-emerging as validated bedside techniques for hemodynamic monitoring, such as video microscopes, are becoming available. We review the current understanding of how sepsis induced hypoperfusion with a focus on recent advances in monitoring the microcirculation, and how a proliferation of biomarkers and emerging therapeutic targets may impact future research.

Recent findings

Conventional hemodynamic monitoring systems fail to assess the microcirculation, and it's response to treatment. Lactate and venous oxygen saturations often drive biomarker-guided sepsis management. Visual assessments such as mottling and capillary refill time are often associated with predicting outcomes, but sometimes can have issues with inter-provider reliability. Microcirculatory damage can be observed sublingually and appears to have prognostic value.

Sepsis is associated with changes in the microcirculation that can lead to tissue hypoxia and organ dysfunction. Further studies are needed to validate the usefulness of microcirculatory bedside tools in guiding resuscitative efforts.
Endotheliopathy Is Associated With a 24-Hour Fibrinolysis Phenotype Described by Low TEG Lysis and High d-Dimer After Trauma
Authors: Richter Robert P. , Joiner Danielle M. , Griffin Russell L. , Jansen Jan O. , Kerby Jeffrey D. , Wade Charles E. , Holcomb John B. , Cardenas Jessica C. , Richter Jillian R.
Published: January 2022

Objectives:

Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma.

Background:

The vascular endothelium is a critical regulator of hemostasis and organ function. The relationship between markers of endotheliopathy and fibrinolysis following trauma has not been evaluated.

Methods:

We performed a secondary analysis of prospectively collected biomarker data in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial. We stratified subjects by 24-hour thromboelastography (TEG) percent clot lysis (LY30) and plasma d-dimer (DD) levels and evaluated differences in endotheliopathy biomarkers and clinical outcomes between subjects with one of four 24-hour fibrinolysis phenotypes: LY30 0.9% to 2.9% (LY30norm), LY30 > 2.9% (LY30high), LY30 < 0.9% and low DD (LY30low+DDlow), and LY30 < 0.9% and high DD (LY30low+DDhigh).

Results:

The analysis included 168 subjects with LY30norm, 32 with LY30high, 147 with LY30low+DDlow, and 124 with LY30low+DDhigh. LY30low+DDhigh subjects had greater injury severity and a higher incidence of severe head injury, multiorgan failure (MOF), and mortality than the other phenotypes. All endotheliopathy biomarkers were significantly higher in the LY30low+DDhigh phenotype. Adjusting for injury severity, mechanism, and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30low+DDhigh phenotype. Both endothelial biomarkers were discriminating for MOF. Subjects with thrombomodulin level >9.5 ng/mL and angiopoietin-2 level >3.6 ng/mL accounted for 64% of subjects who developed MOF.

Conclusions:

In a multicenter trauma cohort, subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated DD 24 hours after injury have significantly worse endotheliopathy and clinical outcomes. Our findings support mechanistic evaluations of the role of the endothelium in fibrinolysis dysregulation that may drive late-stage organ injury.
Complexity-Adjusted Learning Curves for Robotic and Laparoscopic Liver Resection
Authors: Krenzien Felix , Benzing Christian , Feldbrügge Linda , Ortiz Galindo Santiago Andres , Hillebrandt Karl , Raschzok Nathanael , Nevermann Nora , Haber Philipp , Malinka Thomas , Schöning Wenzel , Pratschke Johann , Schmelzle Moritz
Published: January 2022

Background:

Minimally invasive liver surgery (MILS) has a high variance in the type of resection and complexity, which has been underestimated in learning curve studies in the past. The aim of this work was to evaluate complexity-adjusted learning curves over time for laparoscopic liver resection (LLR) and robotic liver resection (RLR).

Methods:

Cumulative sum analysis (CUSUM) and complexity adjustment were performed using the Iwate score for LLR and RLR (n = 647). Lowest point of smoothed data was used to capture the cutoff of the increase in complexity. Data were collected retrospectively at the Department of Surgery of the Charité-Universitätsmedizin Berlin.

Results:

A total of 132 RLR and 514 LLR were performed. According to the complexity-adjusted CUSUM analysis, the initial learning phase was reached after 117 for LLR and 93 procedures for RLR, respectively. With increasing experience, the rate of (extended) right hemihepatectomy multiplied from 8.4% to 18.9% for LLR (P = 0.031) and from 21.6% to 58.3% for RLR (P < 0.001). Complication rates remained comparable between both episodes for LLR and RLR (T1 vs T2, P > 0.05). The complexity-adjusted CUSUM analysis demonstrated for blood transfusion, conversion, and operative time an increase during the learning phase (T1), while a steady state was reached in the following (T2).

Conclusions:

The learning phase for MILS after adjusting for complexity is about 4 times longer than assumed in previous studies, which should urge caution.
Context, COVID-19 and comorbidities: exploring emergent directions in syndemics and HIV research
Authors: Logie Carmen H. , Coelho Madelaine , Kohrt Brandon , Tsai Alexander C. , Mendenhall Emily
Published: January 2022

Purpose of review

The purpose of this review is to identify themes across articles that aimed to explore HIV-related syndemics in 2020 and 2021 and to discuss their implications for research on syndemics.

Recent findings

We identified 189 articles on syndemics between 2020 and 2021. Key themes across studies included COVID-19; mental health and psychosocial challenges; substance use; socio-structural factors; protective factors; and methodological approaches. COVID-19's implications for HIV syndemic research were discussed. Mental health and substance use research largely examined linkages with sexual practices or reduced HIV care retention. Researchers examined associations between socio-structural variables (e.g. poverty) and elevated HIV exposure, reduced HIV testing and poorer health. Concepts of water insecurity and ‘ecosyndemics’ were also raised, as was the importance of attending to noncommunicable diseases and comorbidities. Most studies did not assess interactions between health conditions, signalling the need for methodological grounding in the foundational concepts of syndemic theory.

Most studies recommended that HIV prevention and care research attend to the interplay between poor mental health, substance use and multidimensional violence. Increased attention to structural factors, particularly exacerbated poverty in the COVID-19 pandemic, is required. Research can identify protective factors to harness to advance HIV prevention and care.
A Primer for Success as an Early Career Academic Plastic Surgeon
Authors: Lin Lawrence O. , Barker Jenny C. , Khansa Ibrahim , Janis Jeffrey E.
Published: January 2022

Background:

The early career academic plastic surgeon strives to be an expert surgeon, an innovative researcher, and an impactful educator. Navigating these challenges is difficult in a healthcare landscape with diminishing public research funding, increasing demand from institutions for clinical productivity, and decreased value of surgical education. To help the junior academic plastic surgeon, this article discusses the fundamental aspects of developing an early academic plastic surgery practice, rooted in clinical care, research, and education.

Methods:

Using published literature, expert opinion, and faculty interviews, the authors prepared this primer for education and guidance of plastic surgery residents considering a career in academic plastic surgery and early career academic plastic surgeons.

Results:

This primer highlights elements important to succeeding as a junior academic plastic surgeon including defining goals and priorities, institutional and financial support, mentorship, education of students and residents, developing a practice niche, promotion and tenure, and social support and burnout.

Conclusion:

The early career academic plastic surgeon can create an environment for academic success with appropriate institutional support, mentorship, personal, and social support, to progress toward promotion while minimizing burnout and professional exhaustion.
Glaucoma Evaluation and Management in Eyes With Boston Type 1 and Aurolab Keratoprostheses in an Indian Cohort
Authors: Senthil Sirisha , Mohamed Ashik , Shanbhag Swapna S. , Durgam Shravya Sri , Bagga Bhupesh , Sangwan Virender S. , Basu Sayan
Published: January 2022

Purpose:

The purpose of this study was to evaluate glaucoma and its management in eyes with Boston type 1 keratoprosthesis (Boston-Kpro) and Aurolab keratoprosthesis (Auro-Kpro) in an Indian cohort.

Methods:

This retrospective comparative case series included 175 eyes of 175 patients who underwent type 1 keratoprosthesis from 2009 until 2017; type 1 Boston-Kpro was performed in 107 eyes (107 patients) and Auro-Kpro in 68 eyes (68 patients). The eyes with <1-month follow-up were excluded, and hence, for the analysis of glaucoma, 62 eyes with Auro-Kpro and 99 eyes with Boston-Kpro were included. Progression was defined as the worsening of optic disc damage/progression by visual field/uncontrolled IOP needing additional medications or glaucoma surgery.

Results:

The post-Kpro mean follow-up was 1.8 ± 1.7 years. After Kpro, overall glaucoma was noted in 61% of eyes (98/161). Preexisting glaucoma was noted in 28% of eyes (45/161), postoperative glaucoma was noted in 33% of eyes (53/161), and 39% of eyes (63/161) did not have glaucoma. Among those with preexisting glaucoma, 49% of eyes (22/45) progressed after Kpro implantation. The proportion of eyes with glaucoma in Auro-Kpro (56.5% of eyes) and Boston-Kpro (63.6% of eyes) was similar (P = 0.46). The Kaplan–Meier curve for cumulative survival (Kpro-retention rate) was similar in eyes with and without glaucoma (83% vs. 76% at 1 year, 72% vs. 70% at 2 years; P = 0.65). A higher number of prior intraocular surgeries (P = 0.04) was significantly associated with risk for postoperative glaucoma.

Conclusions:

Glaucoma was seen in more than half of the eyes with type 1 keratoprosthesis. The presence of glaucoma did not seem to affect the retention of keratoprosthesis. A high rate of postoperative glaucoma and the progression of preexisting glaucoma need close monitoring and appropriate management.