Enhancement of Metal Nanostructure Deposition on Silicon Laser-Induced Periodic Surface Structures by Galvanic Replacement.

We report a chemically motivated, single-step method to enhance metal deposition onto silicon laser-induced periodic surface structures (LIPSSs) using reactive laser ablation in liquid (RLAL). Galvanic replacement (GR) reactions were used in conjunction with RLAL (GR-RLAL) to promote the deposition of Au and Cu nanostructures onto a Si LIPSS. To increase the deposition of Au, sacrificial metals Cu, Fe, and Zn were used; Fe and Zn also enhanced the deposition of Cu. We show that the deposited metal content, surface morphology, and metal crystallite size can be tuned based on the difference in electrochemical potentials of the deposited and sacrificial metal. Compared to the Au and Cu reference samples, GR more than doubled the metal content on the LIPSS and reduced metal crystallite sizes by up to 20%. The ability to tune the metal content and crystalline domain size simultaneously makes GR-RLAL a potentially useful approach in the manufacturing of functional metal-LIPSS materials such as surface-enhanced Raman spectroscopy substrates.

Implementation of Extracorporeal CPR Programs for Out-of-Hospital Cardiac Arrest: Another Tale of Two County Hospitals.

Extracorporeal cardiopulmonary resuscitation (ECPR) is a form of intensive life support that has seen increasing use globally to improve outcomes for patients who experience out-of-hospital cardiac arrest (OHCA). Hospitals with advanced critical care capabilities may be interested in launching an ECPR program to offer this support to the patients they serve; however, to do so, they must first consider the significant investment of resources necessary to start and sustain the program. The existing literature describes many single-center ECPR programs and often focuses on inpatient care and patient outcomes in hospitals with cardiac surgery capabilities. However, building a successful ECPR program and using this technology to support an individual patient experiencing refractory cardiac arrest secondary to a shockable rhythm depends on efficient out-of-hospital and emergency department (ED) management. This article describes the process of implementing 2 intensivist-led ECPR programs with limited cardiac surgery capability. We focus on emergency medical services and ED clinician roles in identifying patients, mobilizing resources, initiation and management of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the ED, and ongoing efforts to improve ECPR program quality. Each center experienced a significant learning curve to reach goals of arrest-to-flow times of cannulation for ECPR. Building consensus from multidisciplinary stakeholders, including out-of-hospital stakeholders; establishing shared expectations of ECPR outcomes; and ensuring adequate resource support for ECPR activation were all key lessons in improving our ECPR programs.

A Practical Solution for Preoxygenation in the Prehospital Setting: A Nonrebreather Mask with Flush Rate Oxygen.

OBJECTIVE: Prehospital clinicians need a practical means of providing adequate preoxygenation prior to intubation. A bag-valve-mask (BVM) can be used for preoxygenation in perfect conditions but is likely to fail in emergency settings. For this reason, many airway experts have moved away from using BVM for preoxygenation and instead suggest using a nonrebreather (NRB) mask with flush rate oxygen.Literature on preoxygenation has suggested that a NRB mask delivering flush rate oxygen (on a 15 L/min O2 regulator, maximum flow, ∼50 L/min) is noninferior to BVM at 15 L/min held with a tight seal. However, in the prehospital setting, where emergency airway management success varies, preoxygenation techniques have not been deeply explored. Our study seeks to determine whether preoxygenation can be optimally performed with NRB at flush rate oxygen. METHODS: We performed a crossover trial using healthy volunteers. Subjects underwent 3-min trials of preoxygenation with NRB mask at 25 L/min oxygen delivered from a portable tank, NRB at flush rate oxygen from a portable tank, NRB with flush rate oxygen from an onboard ambulance tank, and BVM with flush rate oxygen from an onboard ambulance tank. The primary outcome was the fraction of expired oxygen (FeO2). We compared the FeO2 of the BVM-flush to other study groups, using a noninferiority margin of 10%. RESULTS: We enrolled 30 subjects. Mean FeO2 values for NRB-25, NRB-flush ambulance, NRB-flush portable, and BVM-flush were 63% (95% confidence interval [CI] 58-68%), 74% (95%, CI 70-78%), 78% (95%, CI 74-83%), and 80% (95%, CI 75-84%), respectively. FeO2 values for NRB-flush on both portable tank and ambulance oxygen were noninferior to BVM-flush on the ambulance oxygen system (FeO2 differences of 1%, 95% CI -3% to 6%; and 6%, 95% CI 1-10%). FeO2 for the NRB-25 group was inferior to BVM-flush (FeO2 difference 16%, 95% CI 12-21%). CONCLUSIONS: Among healthy volunteers, flush rate preoxygenation using NRB masks is noninferior to BVM using either a portable oxygen tank or ambulance oxygen. This is significant because preoxygenation using NRB masks with flush rate oxygen presents a simpler alternative to the use of BVMs. Preoxygenation using NRB masks at 25 L/min from a portable tank is inferior to BVM at flush rate.

Feasibility and Safety of Oral Risperidone to Treat Prehospital Agitation.

OBJECTIVE: Agitation is a common prehospital problem and frequently presents without a clear etiology. Given the dynamic environment of the prehospital setting, there has historically been a varied approach to treating agitation with a heavy reliance on parenteral medications. Newer best practice guidelines recommend the incorporation of oral medications to treat patients experiencing agitation. Therefore, we evaluated the use of oral risperidone in a single system after a change in protocol occurred. METHODS: This was conducted as a retrospective chart review of an urban/suburban Emergency Medical Services system over the period of 8 months. The first day this medication was implemented throughout the service was included. Charts were included for selection if they included risperidone oral dissolving tablet (ODT) as a charted medication. The primary outcome was administration of additional medications to treat agitation. Exploratory outcome measures included acceptance of medication, documented injury to paramedics, documented injuries to patients, scene times, and adverse events that could possibly be linked to the medication. RESULTS: A total of 552 records were screened for inclusion. Risperidone was offered to 530 patients and accepted by 512 (96.6%). Of these 512 patients, the median age of included patients was 39 years old (IQR 29-52 years old) with a range of 18-89 years old. Rescue or additional medications for agitation were required in 9 (1.8%) cases. There were a total of 4 (0.8%) potential complications following administration of risperidone. There were no reported assaults with subsequent injuries to prehospital personnel or injuries sustained by patients reported in this study. CONCLUSIONS: Risperidone ODT was found to be a safe and effective medication to treat mild agitation in a large urban and suburban EMS system. The need for additional medications to treat agitation was rare, and there were no documented injuries to either patients or paramedics.

Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

Effect of a person-centred goals-of-care form and clinical communication training on shared decision-making and outcomes in an acute hospital: a prospective longitudinal interventional study.

BACKGROUND: Patients with a life-limiting illness (LLI) requiring hospitalisation have a high likelihood of deterioration and 12-month mortality. To avoid non-aligned care, we need to understand our patients' goals and values. AIM: To describe the association between the implementation of a shared decision-making (SDM) programme and documentation of goals of care (GoC) for hospitalised patients with LLI. METHODS: A prospective longitudinal interventional study of patients admitted to acute general medicine wards in an Australian tertiary hospital over 5 years was conducted. A SDM programme with a new GoC form, communication training and clinical support was implemented. The primary outcome was the proportion of patients with a documented person-centred GoC discussion (PCD). Clinical outcomes included hospital utilisation and 90-day mortality. RESULTS: 1343 patients were included. The proportion of patients with PCDs increased from 0% to 35.4% (adjusted odds ratio (aOR), 2.38; 95% confidence interval (CI), 2.01-2.82; P < 0.001). During this time, median hospital length of stay decreased from 8 days (interquartile range (IQR), 4-14) to 6 days (IQR, 3-11) (adjusted estimate effect, -0.38; 95% CI, -0.64 to -0.11; P = 0.005) and rapid response team activation from 28% to 13% (aOR, 0.87; 95% CI, 0.78-0.97; P value = 0.01). Documented treatment preference of high-dependency unit care decreased from 39.7% to 24.4% (aOR, 0.81; 95% CI, 0.73-0.89; P value < 0.001), and ward-based care increased from 31.9% to 55.1% (aOR, 1.24; 95% CI, 1.14-1.36; P value < 0.001). CONCLUSION: The implementation of a SDM programme was associated with increased documentation of person-centred GoC, changed patient treatment preference to lower intensity care and reduced hospital utilisation.

Prehospital Ultrasound Diagnosis of Massive Pulmonary Embolism by Non-Physicians: A Case Series.

Massive pulmonary embolism (hemodynamically unstable, defined as systolic BP <90 mmHg) has significant morbidity and mortality. Point of care ultrasound (POCUS) has allowed clinicians to detect evidence of massive pulmonary embolism much earlier in the patient's clinical course, especially when patient instability precludes computerized tomography confirmation. POCUS detection of massive pulmonary embolism has traditionally been performed by physicians. This case series demonstrates four cases of massive pulmonary embolism diagnosed with POCUS performed by non-physician prehospital personnel.

Phosphodiesterase 1C integrates store-operated calcium entry and cAMP signaling in leading-edge protrusions of migrating human arterial myocytes.

In addition to maintaining cellular ER Ca2+ stores, store-operated Ca2+ entry (SOCE) regulates several Ca2+-sensitive cellular enzymes, including certain adenylyl cyclases (ADCYs), enzymes that synthesize the secondary messenger cyclic AMP (cAMP). Ca2+, acting with calmodulin, can also increase the activity of PDE1-family phosphodiesterases (PDEs), which cleave the phosphodiester bond of cAMP. Surprisingly, SOCE-regulated cAMP signaling has not been studied in cells expressing both Ca2+-sensitive enzymes. Here, we report that depletion of ER Ca2+ activates PDE1C in human arterial smooth muscle cells (HASMCs). Inhibiting the activation of PDE1C reduced the magnitude of both SOCE and subsequent Ca2+/calmodulin-mediated activation of ADCY8 in these cells. Because inhibiting or silencing Ca2+-insensitive PDEs had no such effects, these data identify PDE1C-mediated hydrolysis of cAMP as a novel and important link between SOCE and its activation of ADCY8. Functionally, we showed that PDE1C regulated the formation of leading-edge protrusions in HASMCs, a critical early event in cell migration. Indeed, we found that PDE1C populated the tips of newly forming leading-edge protrusions in polarized HASMCs, and co-localized with ADCY8, the Ca2+ release activated Ca2+ channel subunit, Orai1, the cAMP-effector, protein kinase A, and an A-kinase anchoring protein, AKAP79. Because this polarization could allow PDE1C to control cAMP signaling in a hyper-localized manner, we suggest that PDE1C-selective therapeutic agents could offer increased spatial specificity in HASMCs over agents that regulate cAMP globally in cells. Similarly, such agents could also prove useful in regulating crosstalk between Ca2+/cAMP signaling in other cells in which dysregulated migration contributes to human pathology, including certain cancers.

Prehospital Pericardiocentesis Using a Pneumothorax Needle.

Case: We discuss a patient with a penetrating knife wound to the chest who lost pulses from cardiac tamponade. Prehospital ultrasound was able to quickly identify the tamponade and a pericardiocentesis was performed using a Simplified Pneumothorax Emergency Air Release (SPEARTM) Needle (North American Rescue, LLC, USA) with subsequent return of spontaneous circulation. Discussion: Penetrating chest trauma carries significant morbidity and mortality. In traumatic cardiac arrest due to a penetrating mechanism, it is paramount that the patient be transported to a trauma center as quickly as possible. Prehospital pericardiocentesis is a potential life-saving intervention.

Maternal Risk Modeling in Critical Care-Development of a Multivariable Risk Prediction Model for Death and Prolonged Intensive Care.

OBJECTIVES: We aimed to develop and validate an accurate risk prediction model for both mortality and a combined outcome of mortality and morbidity for maternal admissions to critical care. DESIGN: We used data from a high-quality prospectively collected national database, supported with literature review and expert opinion. We tested univariable associations between each risk factor and outcome. We then developed two separate multivariable logistic regression models for the outcomes of acute hospital mortality and death or prolonged ICU length of stay. We validated two parsimonious risk prediction models specific for a maternal population. SETTING: The Intensive Care National Audit and Research Centre Case Mix Programme is the national clinical audit for adult critical care in England, Wales, and Northern Ireland. PATIENTS: All female admissions to adult general critical care units, for the period January 1, 2007-December 31, 2016, 16-50 years old, and admitted either while pregnant or within 42 days of delivery-a cohort of 15,480 women. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We aimed to develop and validate an accurate risk prediction model for both mortality and a combined outcome of mortality and morbidity for maternal admissions to critical care. For the primary outcome of acute hospital mortality, our parsimonious risk model consisting of eight variables had an area under the receiver operating characteristic of 0.96 (95% CI, 0.91-1.00); these variables are commonly available for all maternal admissions. For the secondary composite outcome of death or ICU length of stay greater than 48 hours, the risk model consisting of 17 variables had an area under the receiver operating characteristic of 0.80 (95% CI, 0.78-0.83). CONCLUSIONS: We developed risk prediction models specific to the maternal critical care population. The models compare favorably against general adult ICU risk prediction models in current use within this population.

Don't forget shared decision-making in the COVID-19 crisis.

Mechanical ventilation as a resource is limited and may lead to poor outcomes in at-risk populations. Critical care supports may not be preferred by those at risk of deterioration in the COVID-19 setting. Patient-centred communication and shared decision-making should continue to remain central to clinical practice.

Emergency Department Management of Out-of-Hospital Laryngeal Tubes.

STUDY OBJECTIVE: Laryngeal tubes are commonly used by emergency medical services (EMS) personnel for out-of-hospital advanced airway management. The emergency department (ED) management of EMS-placed laryngeal tubes is unknown. We seek to describe ED airway management techniques, success, and complications of patients receiving EMS laryngeal tubes. METHODS: Using a keyword text search of ED notes, we identified patients who arrived at our ED with a laryngeal tube from 2010 through 2017. We performed structured chart and video reviews for all eligible patients. In our ED, emergency physicians perform all airway management, and there is no protocol dictating airway management for patients arriving with a laryngeal tube. Using descriptive methods, we report the techniques, success, and complications of ED airway management. RESULTS: We analyzed data on 647 patients receiving out-of-hospital laryngeal tubes, including 472 (73%) with cardiac arrest from medical causes, 75 (21%) with cardiac arrest from trauma, and 100 (15%) with other conditions. For 580 patients (89%), emergency physicians exchanged the laryngeal tube for a definitive airway in the ED. Of the 67 patients not intubated in the ED, 66 died in the ED without further airway management. Of the 580 patients intubated in the ED, orotracheal intubation was the first method attempted for 578 (>99%) and was successful on the first attempt for 515 of 578 (89%). Macintosh video laryngoscopy (88% of initial attempts) and a bougie (68% of initial attempts) were commonly used adjuncts. For 345 of 578 patients (60%), the laryngeal tube was removed before intubation attempts. For 112 of 578 patients (19%), the first intubation attempt occurred with the deflated laryngeal tube left in place. Three patients (<1%) required a surgical airway. CONCLUSION: In this cohort, emergency physicians successfully exchanged an out-of-hospital laryngeal tube for an endotracheal tube, using commonly available airway management techniques. ED clinicians should be familiar with techniques for exchanging out-of-hospital extraglottic airways for an endotracheal tube.

The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.

Follicular helper T (Tfh) cells provide selection signals to germinal center B cells, which is essential for long-lived antibody responses. High CXCR5 and low CCR7 expression facilitates their homing to B cell follicles and distinguishes them from T helper 1 (Th1), Th2, and Th17 cells. Here, we showed that Bcl-6 directs Tfh cell differentiation: Bcl-6-deficient T cells failed to develop into Tfh cells and could not sustain germinal center responses, whereas forced expression of Bcl-6 in CD4(+) T cells promoted expression of the hallmark Tfh cell molecules CXCR5, CXCR4, and PD-1. Bcl-6 bound to the promoters of the Th1 and Th17 cell transcriptional regulators T-bet and RORgammat and repressed IFN-gamma and IL-17 production. Bcl-6 also repressed expression of many microRNAs (miRNAs) predicted to control the Tfh cell signature, including miR-17-92, which repressed CXCR5 expression. Thus, Bcl-6 positively directs Tfh cell differentiation, through combined repression of miRNAs and transcription factors.

Septic shock resuscitation in the first hour.

PURPOSE OF REVIEW: We reviewed the recent advances in the initial approach to resuscitation of sepsis and septic shock patients. RECENT FINDINGS: Sepsis and septic shock are life-threatening emergencies. Two key interventions in the first hour include timely antibiotic therapy and resuscitation. Before any laboratory results, the need for resuscitation is considered if a patient with suspected infection has low blood pressure (BP) or impaired peripheral circulation found at clinical examination. Until now, this early resuscitation in sepsis and septic shock was supported by improvements in outcome seen with goal-directed therapy. However, three recent, goal-directed therapy trials failed to replicate the originally reported mortality reductions, prompting a debate on how this early resuscitation should be performed. As resuscitation is often focussed on macrociculatory goals such as optimizing central venous pressure, the discordance between microcirculatory and macrocirculatory optimization during resuscitation is a potential argument for the lack of outcome benefit in the newer trials. Vasoactive drug dose and large volume resuscitation-associated-positive fluid balance, are independently associated with worse clinical outcomes in critically ill sepsis and septic shock patients. As lower BP targets and restricted volume resuscitation are feasible and well tolerated, should we consider a lower BP target to reduce the adverse effects of catecholamine' and excess resuscitation fluids. Evidence guiding fluids, vasopressor, and inotrope selection remains limited. SUMMARY: Though the early resuscitation of sepsis and septic shock is key to improving outcomes, ideal resuscitation targets are elusive. Distinction should be drawn between microcirculatory and macrocirculatory changes, and corresponding targets. Common components of resuscitation bundles such as large volume resuscitation and high-dose vasopressors may not be universally beneficial. Microcirculatory targets, individualized resuscitation goals, and reassessment of completed trials using the updated septic shock criteria should be focus areas for future research.

Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial.

IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007). CONCLUSIONS AND RELEVANCE: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01151865.

Training as imagined? A critical realist analysis of Scotland's internal medicine simulation programme.

BACKGROUND: Evaluating the impact of simulation-based education (SBE) has prioritised demonstrating a causal link to improved patient outcomes. Recent calls herald a move away from looking for causation to understanding 'what else happened'. Inspired by Shorrock's varieties of human work from patient safety literature, this study draws on the concept of work-as-done versus work-as-imagined. Applying this to SBE recognises that some training impacts will be unexpected, and the realities of training will never be quite as imagined. This study takes a critical realist stance to explore the experience and consequences, intended and unintended, of the internal medicine training (IMT) simulation programme in Scotland, to better understand 'training-as-done'. METHODS: Critical realism accepts that there is a reality to uncover but acknowledges that our knowledge of reality is inevitably our construction and cannot be truly objective. The IMT simulation programme involves three courses over a 3-year period: a 3-day boot camp, a skills day and a 2-day registrar-ready course. Following ethical approval, interviews were conducted with trainees who had completed all courses, as well as faculty and stakeholders both immersed in and distant from course delivery. Interviews were audio-recorded, transcribed verbatim and analysed using critical realist analysis, influenced by Shorrock's proxies for work-as-done. RESULTS: Between July and December 2023, 24 interviews were conducted with ten trainees, eight faculty members and six stakeholders. Data described proxies for training-as-done within three broad categories: design, experience and impact. Proxies for training design included training-as-prescribed, training-as-desired and training-as-prioritised which compete to produce training-as-standardised. Experience included training-as-anticipated with pre-simulation anxiety and training-as-unintended with the valued opportunity for social comparison as well as a sense of identity and social cohesion. The impact reached beyond the individual trainee with faculty development and inspiration for other training ventures. CONCLUSION: Our findings highlight unintended consequences of SBE such as social comparison and feeling 'valued as a trainee, valued as a person'. It sheds light on the fear of simulation, reinforcing the importance of psychological safety. A critical realist approach illuminated the 'bigger picture', revealing insights and underlying mechanisms that allow this study to present a new framework for conceptualising training evaluation.

The land degradation and desertification-socioeconomic nexus in Egypt's delta region: A case study on Alexandria and Beheira.

The Nile Delta is Egypt's primary source of agricultural production. However, the Delta's capacity to remain Egypt's vital source of food security, rural development and economic stability is diminishing amidst persistent climate change risks. In this regard, this research gauges the impacts of climatic and anthropogenic factors on agricultural revenues and household wealth in Alexandria and Beheira, two of the Delta's most climate-vulnerable governorates. The research employs the Ricardian model by applying Seemingly Unrelated Regressions (SUR), to test the impacts of climate change on real revenues from agriculture. Results show that quadratic temperature negatively impacts revenues from agriculture in Alexandria, while employment in agriculture, irrigation, livestock and machines positively contribute to revenues. In Beheira, results show that temperature and machines negatively contribute to agricultural revenues, while livestock contributes positively. The research further estimates the socioeconomic impacts of land degradation and desertification on individuals in Alexandria and Beheira by using Ordinary Least Squares (OLS) robust standard errors. Individuals' socio-economic status, proxied by their wealth index (WI), is regressed on the Environmental Sensitivity Index (ESI), gender, age, education, household size, work in agriculture and rural/urban residence. Outcomes reveal that individuals' wealth status in Alexandria is positively correlated with ESI, age, and education. In Beheira, land degradation, household size, rural areas and fathers working in agriculture are negatively correlated with wealth. Education, however, contributes positively to wealth. The study proposes policy implications that aim to foster the growth and development of rural residents in the Delta region.

Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA.

Immune responses are normally targeted against microbial pathogens and not self-antigens by mechanisms that are only partly understood. Here we define a newly discovered pathway that prevents autoimmunity by limiting the levels on T lymphocytes of aco-stimulatory receptor, the inducible T-cell co-stimulator(ICOS). In sanroque mice homozygous for an M199R mutation in the ROQ domain of Roquin (also known as Rc3h1), increased Icos expression on T cells causes the accumulation of lymphocytes that is associated with a lupus-like autoimmune syndrome. Roquin normally limits Icos expression by promoting the degradation of Icos messenger RNA.A conserved segment in the unusually long ICOS 3' untranslated mRNA is essential for regulation by Roquin. This segment comprises a 47-base-pair minimal region complementary to T-cell-expressed microRNAs including miR-101, the repressive activity of which is disrupted by base-pair inversions predicted to abrogate miR-101 binding. These findings illuminate a critical post-transcriptional pathway within T cells that regulates lymphocyte accumulation and autoimmunity, and highlights the therapeutic potential of partially antagonising the ICOS pathway.

Integrating climate change in Environmental Impact Assessment: A review of requirements across 19 EIA regimes.

The contribution of human activities to climate change is well understood. Yet the integration of climate change considerations into local decision making tools designed to govern activities affecting the environment, such as Environmental Impact Assessments (EIAs), remains underdeveloped and inconsistently applied for proposed policies, programs, plans and projects. This study reviews progress across a range of 19 EIA regimes and identifies and assesses regulations and guidelines that have been established to promote the integration of climate change considerations within EIAs. A typology of levels of integration is developed to guide analysis across multiple EIA regimes. The findings identify a global and growing requirement for climate change aspects to be considered within EIAs and describe the range of ways this is done across the regimes selected. Climate change is typically concerned with the mitigation of greenhouse gas emissions from proposed developments in EIAs. Fewer regimes are concerned with climate change adaptation, and in general, an integration deficit is identified for regimes where climate change is only partially considered. Examples of high integration indicate that EIA holds the potential to play a substantive role in climate change governance at project level decision making, suggesting the tools hold promise for local level climate governance. However, many domestic obstacles can militate against integration, including political, socio-technical, and economic imperatives, particularly for exemptions of sector and scope. Nevertheless, examples also indicate advances can be made through jurisprudence during the EIA review stage to establish new precedents of how climate should be considered in EIAs. Potential future research and practice directions are identified, and recommendations include the development of regulations and practice guidelines; inclusion of climate change adaptation; strengthening post-decision monitoring; application to all relevant sectors and activities; alignment with SEA; and integration across all stages of the EIA process.

Extracorporeal membrane oxygenation versus conventional rewarming for severe hypothermia in an urban emergency department.

BACKGROUND: Severe hypothermia (core body temperature < 28°C) is life-threatening and predisposes to cardiac arrest. The comparative effectiveness of different active internal rewarming methods in an urban U.S. population is unknown. We aim to compare outcomes between hypothermic emergency department (ED) patients rewarmed conventionally using an intravascular rewarming catheter or warm fluid lavage versus those rewarmed using extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective cohort analysis of adults with severe hypothermia due to outdoor exposure presenting to an urban ED in Minnesota, 2007-2021. The primary outcome was hospital survival. We also calculated the rewarming rate in the 4 h after ED arrival and compared these data between patients rewarmed with ECMO (the extracorporeal rewarming group) versus without ECMO (the conventional rewarming group). We repeated these analyses in the subgroup of patients with cardiac arrest. RESULTS: We analyzed 44 hypothermic ED patients: 25 patients in the extracorporeal rewarming group (median temperature 24.1°C, 84% with cardiac arrest) and 19 patients in the conventional rewarming group (median temperature 26.3°C, 37% with cardiac arrest; 89% received an intravascular rewarming catheter). The median rewarming rate was greater in the extracorporeal versus conventional group (2.3°C/h vs. 1.5°C/h, absolute difference 0.8°C/h, 95% confidence interval [CI] 0.3-1.2°C/h) yet hospital survival was similar (68% vs. 74%). Among patients with cardiac arrest, hospital survival was greater in the extracorporeal versus conventional group (71% vs. 29%, absolute difference 42%, 95% CI 4%-82%). CONCLUSIONS: Among ED patients with severe hypothermia and cardiac arrest, survival was significantly higher with ECMO versus conventional rewarming. Among all hypothermic patients, ECMO use was associated with faster rewarming than conventional methods.