Delineating the conformational landscape of the adenosine A2A receptor during G protein coupling.

G-protein-coupled receptors (GPCRs) represent a ubiquitous membrane protein family and are important drug targets. Their diverse signaling pathways are driven by complex pharmacology arising from a conformational ensemble rarely captured by structural methods. Here, fluorine nuclear magnetic resonance spectroscopy (19F NMR) is used to delineate key functional states of the adenosine A2A receptor (A2AR) complexed with heterotrimeric G protein (Gαsß1γ2) in a phospholipid membrane milieu. Analysis of A2AR spectra as a function of ligand, G protein, and nucleotide identifies an ensemble represented by inactive states, a G-protein-bound activation intermediate, and distinct nucleotide-free states associated with either partial- or full-agonist-driven activation. The Gßγ subunit is found to be critical in facilitating ligand-dependent allosteric transmission, as shown by 19F NMR, biochemical, and computational studies. The results provide a mechanistic basis for understanding basal signaling, efficacy, precoupling, and allostery in GPCRs.

Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Regulated Restructuring of Mucins During Secretory Granule Maturation In Vivo.

Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (Vha16-1), Ca2+ ions (fwe) and Cl- ions (Clic and ClC-c). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of mucins through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct mucins are efficiently packaged into and secreted from secretory granules may provide insight into diseases resulting from defects in mucin secretion.

An Ultra-Flexible Sodium-Ion Full Cell with High Energy/Power Density and Unprecedented Structural Stability.

Futuristic wearable electronics desperately need power sources with similar flexibility and durability. In this regard, the authors, therefore, propose a scalable PAN-PMMA blend-derived electrospinning protocol to fabricate free-standing electrodes comprised of cobalt hexacyanoferrate nanocube cathode and tin metal organic framework-derived nanosphere anode, respectively, for flexible sodium-ion batteries. The resulting unique inter-networked nanofiber mesh offers several advantages such as robust structural stability towards repeated bending and twisting stresses along with appreciable electronic/ionic conductivity retention without any additional post-synthesis processing. The fabricated flexible sodium ion full cells deliver a high working voltage of 3.0 V, an energy density of 273 Wh·kg-1 , and a power density of 2.36 kW·kg-1 . The full cells retain up to 86.73% of the initial capacity after 1000 cycles at a 1.0 C rate. After intensive flexibility tests, the full cells also retain 78.26% and 90.78% of the initial capacity after 1000 bending and twisting cycles (5 mm radius bending and 40o axial twisting), respectively. This work proves that the proposed approach can also be employed to construct similar robust, free-standing nanofiber mesh-based electrodes for mass-producible, ultra-flexible, and durable sodium ion full cells with commercial viability.

Triphasic Ni2P-Ni12P5-Ru with Amorphous Interface Engineering Promoted by Co Nano-Surface for Efficient Water Splitting.

This research designs a triphasic Ni2P-Ni12P5-Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@NimPn-Ru) to form a hierarchical 3D interconnected architecture. The Co@NimPn-Ru material promotes unique reactivities toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. The material delivers an overpotential of 30 mV for HER at 10 mA cm-2 and 320 mV for OER at 50 mA cm-2 in freshwater. The electrolyzer cell derived from Co@NimPn-Ru(+,-) requires a small cell voltage of only 1.43 V in alkaline freshwater or 1.44 V in natural seawater to produce 10 mA cm-2 at a working temperature of 80 °C, along with high performance retention after 76 h. The solar energy-powered electrolyzer system also shows a prospective solar-to-hydrogen conversion efficiency and sufficient durability, confirming its good potential for economic and sustainable hydrogen production. The results are ascribed to the synergistic effects by an exclusive combination of multi-phasic crystalline Ni2P, Ni12P5, and Ru clusters in presence of amorphous phosphate interface attached onto cobalt nano-surface, thereby producing rich exposed active sites with optimized free energy and multi open channels for rapid charge transfer and ion diffusion to promote the reaction kinetics.

Ru Single Atom Dispersed on MoS2/MXene for Enhanced Sulfur Reduction Reaction in Lithium-Sulfur Batteries.

The high theoretical energy density (2600 Wh kg-1) and low cost of lithium-sulfur batteries (LSBs) make them an ideal alternative for the next-generation energy storage system. Nevertheless, severe capacity degradation and low sulfur utilization resulting from shuttle effect hinder their commercialization. Herein, Single-atom Ru-doped 1T/2H MoS2 with enriched defects decorates V2C MXene (Ru-MoS2/MXene) produced by a new phase-engineering strategy employed as sulfur host to promote polysulfide adsorption and conversion reaction kinetics. The Ru single atom-doped adjusts the chemical environment of the MoS2/MXene to anchor polysulfide and acts as an efficient center to motivate the redox reaction. In addition, the rich defects of the MoS2 and ternary boundary among 1T/2H MoS2 and V2C accelerate the charge transfer and ion movements for the reaction. As expected, the Ru-MoS2/MXene/S cathode-based cell exhibits a high-rate capability of 684.3 mAh g-1 at 6 C. After 1000 cycles, the Ru-MoS2/MXene/S cell maintains an excellent cycling stability of 696 mAh g-1 at 2 C with a capacity degradation as low as 0.02% per cycle. Despite a high sulfur loading of 9.5 mg cm-2 and a lean electrolyte-to-sulfur ratio of 4.3, the cell achieves a high discharge capacity of 726 mAh g-1.

A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

The Association between Red Blood Cell Distribution Width and Mortality Risk after Hip Fracture: A Meta-Analysis.

Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.

Health-related quality of life in patients with extremity bone sarcoma after surgical treatment: a systematic review.

PURPOSE: We conducted a systematic review of studies reporting on measurement of health-related quality of life (HRQoL), with a special focus on the use of the preference-weighted instruments, in patients with extremity bone sarcoma treated with limb-salvage surgery or amputation. METHODS: We searched MedLine, Embase, Cochrane Library and Web of Science for English-language studies reporting on HRQoL of patients with bone sarcoma from inception to 28 August 2023. All records found were independently reviewed by two reviewers. We used the Newcastle-Ottawa Scale (NOS) and the CONSORT 2010 checklist to assess the quality of the cohort and randomised studies, respectively. RESULTS: The search identified 1225 records, of which 16 studies were included for data extraction. Only one study used a preference-weighted instrument for measuring HRQoL in a small sample of patients (n = 28). Ten studies used the generic SF-36 questionnaire, but no preference-weighted HRQoL based on SF-6D was derived from the SF-36 scores. Most studies comparing HRQoL between amputation and limb-salvage surgery reported no significant differences. Twelve cohort studies scored six or more out of nine points based on the NOS. The only randomised study scored 54% on the CONSORT 2010 checklist. CONCLUSIONS: The approaches used to measure HRQoL were inconsistent and outcome scores varied substantially. Only one study used preference-weighted instruments for HRQoL measurement. Future research into the surgical treatment of extremity bone sarcoma should consider the use of preference-weighted instruments to measure HRQoL, which will therefore enable economic evaluation for the growing orthopaedic armamentarium of novel surgical interventions. REGISTRATION: This systematic review was registered with the PROSPERO International prospective register of systematic reviews (CRD42021282380).

Understanding the measurement relationship between EQ-5D-5L, PROMIS-29 and PROPr.

PURPOSE: Many generic patient-reported instruments are available for the measurement of health outcomes, including EQ-5D-5L, and the Patient-Reported Outcome Measurement Information System (PROMIS). Assessing their measurement characteristics informs users about the consistency between, and limits of, evidence produced. The aim was to assess the measurement relationship between the EQ-5D-5L descriptive system and value sets, the PROMIS-29 and PROPr (PROMIS value set). METHODS: Data were extracted from a cross-sectional survey administering measures of quality of life online in Australia. Descriptive analysis, agreement and construct validity assessment methods were used to compare instruments at the item, domain and value set level. RESULTS: In total, 794 Australians completed the survey. Convergent validity analysis found that similar dimensions across instruments were highly correlated (> 0.50), but the PROMIS-29 assesses additional health concepts not explicitly covered by EQ-5D (sleep and fatigue). Known-group assessment found that EQ-5D-5L and PROPr were able to detect those with and without a condition (ES range 0.78-0.83) but PROPr could more precisely detect differing levels of self-reported health. Both instruments were sensitive to differences in levels of pain. DISCUSSION: There is some consistency in what the EQ-5D-5L, PROMIS-29 and PROPr measure. Differences between value set characteristics can be linked to differences what is measured and the valuation approaches used. This has implications for the use of each in assessing health outcomes, and the results can inform decisions about which instrument should be used in which context.

Telehealth in oncology: a cost analysis to evaluate the financial impact of implementing regional trial hubs within a phase 3 cancer clinical trial.

This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity.

Does Clockwise Rotation of Maxillomandibular Complex Using Surgery-First Approach to Correct Mandibular Prognathism Affect Surgical Movement and Stability?

PURPOSE: Orthognathic surgery (OGS) using the surgery-first approach (SFA) can decrease treatment time and increase patient satisfaction. Clockwise rotation (CWR) of the maxillomandibular complex to correct mandibular prognathism leads to optimized functional, aesthetic, and stable outcomes. This study examined the combined effect of SFA and CWR of the maxillomandibular complex to correct mandibular prognathism by comparing the surgical movement before (T0) and immediately after OGS (T1) and the stability between T1 and 12 months after OGS (T2). METHODS: This prospective cohort study enrolled patients with skeletal Class III malocclusion who underwent SFA involving Le Fort I osteotomy and bilateral sagittal split osteotomy, with or without genioplasty. Based on the occlusal plane (OP) change at T0-T1, the patients were divided into CWR (OP > 4°) and control (C) groups (OP ≤ 4°). The predictor variable was OP change at T0-T1. The primary outcome variable was the stability of pogonion (Pog) at T1-T2. The covariates included demographic factors, cephalometric measurements (anterior facial height, posterior facial height, OP, mandibular plane angle, incisor mandibular plane angle, overjet, and overbite), and 3-dimensional landmark displacement (anterior nasal spine, A-point, upper central incisor, upper first molar, lower central incisor, lower first molar, Pog, gonion, and condylion). An independent t-test was used to compare between these 2 groups when appropriate. The level of significance was set at P < .05. RESULTS: The sample included 28 patients (17 females) in the C group and 36 (24 females) in the CWR group; the mean ages were 23.89 ± 3.35 and 24.08 ± 4.02 years, respectively. For the surgical movement at T0-T1, the CWR group showed an association with vertical movement of the maxilla at posterior nasal spine (P = .005), anterior nasal spine (P < .001), and A-point (P < .001) and horizontal backward movement of the mandible at B-point (P < .001), Pog (P < .001), and gonion (P = .042). At T1-T2, all landmarks remained stable without clinically significant difference between the 2 groups. CONCLUSION: Surgical movement in the CWR group could vertically displace the maxilla and setback mandible more than that in the C group. Postoperative skeletal stability remained the same between the 2 groups at 1 year after OGS.

Does Clockwise Rotation of Maxillomandibular Complex Using Surgery-First Approach to Correct Mandibular Prognathism Improve Facial Appearance?

BACKGROUND: Facial aesthetics may be optimized based on a deeper understanding of soft tissue changes after orthognathic surgery. PURPOSE: The purpose of the study was to delineate facial soft tissue changes after clockwise rotation (CWR) of the maxillomandibular complex (MMC) to correct mandibular prognathism using the surgery-first approach. STUDY DESIGN, SETTING, SAMPLE: This prospective cohort study enrolled patients over 18 years of age with skeletal Class III malocclusion in the craniofacial center. The patients were excluded with previous history of craniofacial syndrome, orthognathic surgery trauma, infection at surgical sites, chin deviation (menton deviation ≥4 mm), 2 or more missing data points after surgery, or without informed consent. This study compared significant facial changes before (T0) and after orthodontic debonding (T1) in the CWR and control groups. PREDICTOR VARIABLE: The patients were divided in accordance with maxillary occlusal plane change (OPC) after surgery into CWR (OPC >4°) and control (OPC ≤4°) groups. MAIN OUTCOME VARIABLE: The primary outcome variable was frontal lip curvature (FLC: Right Cheilion-Stomion-Left Cheilion, degree) with or without upper lip curving upward at T1, where upper lip curving upward was considered more favorable. COVARIATES: The covariates included age, sex, and various cephalometric measurements. ANALYSES: The Mann-Whitney U test, paired, and independent t-test were implemented to compare the intragroup and intergroup differences. Statistical significance was indicated by P value <.05. RESULTS: The study comprised 34 patients (21 women) in the control group and 37 (29 women) in the CWR group; their mean ages were 23.64 ± 4.38 and 24.21 ± 3.84 years, respectively (P value = .562). At T1, the CWR group had significant increased FLC (P value = .001), alar width (P value = .034), and lower vermilion height (P value = .018), and decreased lower lip length (P value = .004). The high FLC group had significant decreased upper lip projection (P value = .002) and increased nasolabial angle (P value = .013). The significant relationship between CWR and high FLC was supported by the χ2 test (P value = .018) and multiple logistic regression (P value = .017). CONCLUSION: Greater CWR of the MMC increased FLC and lower vermilion height and reduced lower lip length. High FLC resulting from the CWR of the MMC improved facial appearance by moving the upper lip curve upward.

Integrated Platform Addressing the Finger-Prick Blood Processing Challenges of Point-of-Care Electrical Biomarker Testing.

Continued advances in label-free electrical biosensors pave the way to simple, rapid, cost-effective, high-sensitivity, and quantitative biomarker testing at the point-of-care setting that would profoundly transform healthcare. However, implementation in routine diagnostics is faced with significant challenges associated with the inherent requirement for biofluid sample processing before and during testing. We present here a simple yet robust autonomous finger-prick blood sample processing platform integrated with nanoscale field-effect transistor biosensors and demonstrate the feasibility of measuring the SARS-CoV-2 nucleocapsid protein. The 3D-printed platform incorporates a high-yield blood-to-plasma separation module and a delay valve designed to terminate the assay at a specific time. The platform is driven by hydrostatic pressure to efficiently and automatically dispense plasma and washing/measurement buffer to the nanosensors. Our model study demonstrates the feasibility of detecting down to 1.4 pg/mL of the SARS-CoV-2 nucleocapsid protein within 25 min and with only minimal operator intervention.

Structure of MotA, a flagellar stator protein, from hyperthermophile.

Many motile bacteria swim and swarm toward favorable environments using the flagellum, which is rotated by a motor embedded in the inner membrane. The motor is composed of the rotor and the stator, and the motor torque is generated by the change of the interaction between the rotor and the stator induced by the ion flow through the stator. A stator unit consists of two types of membrane proteins termed A and B. Recent cryo-EM studies on the stators from mesophiles revealed that the stator consists of five A and two B subunits, whereas the low-resolution EM analysis showed that purified hyperthermophilic MotA forms a tetramer. To clarify the assembly formation and factors enhancing thermostability of the hyperthermophilic stator, we determined the cryo-EM structure of MotA from Aquifex aeolicus (Aa-MotA), a hyperthermophilic bacterium, at 3.42 Å resolution. Aa-MotA forms a pentamer with pseudo C5 symmetry. A simulated model of the Aa-MotA5MotB2 stator complex resembles the structures of mesophilic stator complexes, suggesting that Aa-MotA can assemble into a pentamer equivalent to the stator complex without MotB. The distribution of hydrophobic residues of MotA pentamers suggests that the extremely hydrophobic nature in the subunit boundary and the transmembrane region is a key factor to stabilize hyperthermophilic Aa-MotA.

A Flexible and Transparent Zinc-Nanofiber Network Electrode for Wearable Electrochromic, Rechargeable Zn-Ion Battery.

The flexible electrochromic Zn-ion battery (FE-ZiB), a newly born energy-storage technology having both electrochromic characteristics and energy-storage capability in a single device, will be a promising technology for the future transparent wearable electronics. However, the current technology limits the fabrication of FE-ZIB because the zinc (Zn) anode material is opaque and rigid. The development of a flexible and transparent Zn anode is the key factor to overcoming the current limitation. Here, for the first time, a flexible, transparent zinc-nanofiber network anode electrode (Zn@Ni@AgNFs) is reported for an FE-ZiB device that yields a remarkable electrochemical performance of a high areal capacity of 174.82 mA h m2 at 0.013 mA cm-2 applied current density, high optical contrast (50%), and excellent mechanical flexibility. The fabricated FE-ZiB device also exhibits a high volumetric energy density of 378.8 W h m-3 at a power density of 562.7 W m-3 . Besides, the FE-ZiB demonstrates excellent electrochromic capability with a reversible color transition from a transparent in a discharged state (0.3 V) to a dark bluish-violet in a charged state (1.6 V). These results highlight a new pathway for the development of transparent batteries for smart wearable electronic devices.

The comparative mortality of an elite group in the long run of history: an observational analysis of politicians from 11 countries.

This study aims to compare the mortality rate and life expectancy of politicians with those of the age and gender-matched general populations. This was an observational analysis of mortality rates of politicians (i.e. members of national parliaments with available data on dates of birth, death and election, gender, and life tables) in 11 developed countries. Politicians were followed from date of first election until either death or the last available year with life table data. Relative mortality differences were estimated using standardised mortality ratios (SMRs). Absolute inequalities were quantified as the difference in survival by deducting a population's remaining life expectancy from politicians' remaining life expectancy at age 45, estimated using Gompertz parametric proportional hazards models. We included 57,561 politicians (with follow-up ranging from 1816-2016 for France to 1949-2017 for Germany). In almost all countries politicians had similar rates of mortality to the general population in the early part of the twentieth century. Relative mortality and survival differences (favouring politicians) increased considerably over the course of the twentieth century, with recent SMRs ranging from 0.45 (95%CI 0.41-0.50) in Italy to 0.82 (95%CI 0.69-0.95) in New Zealand. The peak life expectancy gaps ranged from 4.4 (95% CI, 3.5-5.4) years in the Netherlands to 7.8 (95% CI, 7.2-8.4) years in the US. Our results show large relative and absolute inequalities favouring politicians in every country. In some countries, such as the US, relative inequalities are at the greatest level in over 150 years.

Evidence on the relationship between PROMIS-29 and EQ-5D: a literature review.

PURPOSE: EQ-5D and PROMIS-29 are both concise, generic measures of patient-reported outcomes accompanied by preference weights that allow the estimation of quality-adjusted life years (QALYs). Both instruments are candidates for use in economic evaluation. However, they have different features in terms of the domains selected to measure respondents' self-perceived health and the characteristics of (and methods used to obtain) the preference weights. It is important to understand the relationship between the instruments and the implications of choosing either for the evidence used in decision-making. This literature review aimed to synthesise existing evidence on the relationship between PROMIS-29 (and measures based on it, such as PROMIS-29+2) and EQ-5D (both EQ-5D-3L and EQ-5D-5L). METHODS: A literature review was conducted in PubMed and Web of Science to identify studies investigating the relationship between PROMIS-29 and EQ-5D-based instruments. RESULTS: The literature search identified 95 unique studies, of which nine studies met the inclusion criteria, i.e. compared both instruments. Six studies examined the relationship between PROMIS-29 and EQ-5D-5L. Three main types of relationship have been examined in the nine studies: (a) comparing PROMIS-29 and EQ-5D as descriptive systems; (b) mapping PROMIS-29 domains to EQ-5D utilities; and (c) comparing and transforming PROMIS-29 utilities to EQ-5D utilities. CONCLUSION: This review has highlighted the lack of evidence regarding the relationship between PROMIS-29 and EQ-5D. The impact of choosing either instrument on the evidence used in cost-effectiveness analysis is currently unclear. Further research is needed to understand the relationship between the two instruments.

A Southeast Asian expert consensus on the management of major depressive disorder with suicidal behavior in adults under 65 years of age.

BACKGROUND: The high prevalence of suicidal behavior among individuals with major depressive disorder (MDD) in Southeast Asia (SEA) underscores the need for optimized management to address depressive symptoms, reduce suicide risk and prevent suicide in these individuals. Given the lack of clear guideline recommendations for assessing and managing these patients, regional consensus-based recommendations which take into account diverse local contexts across SEA may provide useful guidance for clinical practice. METHODS: A narrative literature review and pre-meeting survey were conducted prior to the consensus meeting of an SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with MDD with suicidal behavior. Utilizing the RAND/UCLA Appropriateness Method, the expert panel developed consensus-based recommendations on the assessment and treatment of adult patients with MDD with suicidal behavior under 65 years. RESULTS: Screening of adult patients under 65 years with MDD for suicide risk using both a validated assessment tool and clinical interview is recommended. An improved suicide risk stratification - incorporating both severity and temporality, or using a prevention-focused risk formulation - should be considered. For a patient with an MDD episode with low risk of suicide, use of antidepressant monotherapy, and psychotherapy in combination with pharmacological treatment are both recommended approaches. For a patient with an MDD episode with high risk of suicide, or imminent risk of suicide requiring rapid clinical response, or for a patient who had received adequate AD but still reported suicidal behavior, recommended treatment strategies include antidepressant augmentation, combination use of psychotherapy or electroconvulsive therapy with pharmacological treatment, and inpatient care. Suicide-specific psychosocial interventions are important for suicide prevention and should also be part of the management of patients with MDD with suicidal behavior. CONCLUSIONS: There are still unmet needs in the assessment of suicide risk and availability of treatment options that can deliver rapid response in patients with MDD with suicidal behavior. These consensus recommendations on the management of adult patients with MDD with suicidal behavior under 65 years may serve as a useful guidance in diverse clinical practices across the SEA region. Clinical judgment based on careful consideration of individual circumstances of each patient remains key to determining the most appropriate treatment option.

Metal-Oxide FET Biosensor for Point-of-Care Testing: Overview and Perspective.

Metal-oxide semiconducting materials are promising for building high-performance field-effect transistor (FET) based biochemical sensors. The existence of well-established top-down scalable manufacturing processes enables the reliable production of cost-effective yet high-performance sensors, two key considerations toward the translation of such devices in real-life applications. Metal-oxide semiconductor FET biochemical sensors are especially well-suited to the development of Point-of-Care testing (PoCT) devices, as illustrated by the rapidly growing body of reports in the field. Yet, metal-oxide semiconductor FET sensors remain confined to date, mainly in academia. Toward accelerating the real-life translation of this exciting technology, we review the current literature and discuss the critical features underpinning the successful development of metal-oxide semiconductor FET-based PoCT devices that meet the stringent performance, manufacturing, and regulatory requirements of PoCT.