Thermodynamic Evidence of Structural Transformations in CO2-Loaded Metal-Organic Framework Zn(MeIm)2 from Heat Capacity Measurements.

Metal-organic frameworks are a class of porous compounds with potential applications in molecular sieving, gas sequestration, and catalysis. One family of MOFs, zeolitic imidizolate frameworks (ZIFs), is of particular interest for carbon dioxide sequestration. We have previously reported the heat capacity of the sodalite topology of the zinc 2-methylimidazolate framework (ZIF-8), and in this Article we present the first low-temperature heat capacity measurements of ZIF-8 with various amounts of sorbed CO2. Molar heat capacities from 1.8 to 300 K are presented for samples containing up to 0.99 mol of CO2 per mol of ZIF-8. Samples with at least 0.56 mol of CO2 per mol of ZIF-8 display a large, broad anomaly from 70 to 220 K with a shoulder on the low-temperature side, suggesting sorption-induced structural transitions. We attribute the broad anomaly partially to a gate-opening transition, with the remainder resulting from CO2 rearrangement and/or lattice expansion. The measurements also reveal a subtle anomaly from 0 to 70 K in all samples that does not exist in the sorbate-free material, which likely reflects new vibrational modes resulting from sorbate/ZIF-8 interactions. These results provide the first thermodynamic evidence of structural transitions induced by CO2 sorption in the ZIF-8 framework.

Is Emergency Medicine the Right Choice for Me?

One of the hardest decisions a medical student has to make is the choice of specialty. Many studies have explored what influences the choice of emergency medicine (EM) as a specialty. In this article, we elaborate on the most important incentives, including the diversity in patients' presentations, having a defined and flexible schedule, the plasticity in choosing and changing a practice location, and the acuity of care and trauma experience. Additionally, we tackle some of the challenges that emergency physicians face. For instance, having to follow a different thought process than most other physicians, as well as the patients' quality and expectations. We also address some of the concerns regarding the specialty, specifically burnout, stress, and the fear associated with maintaining a career in EM. Finally, we provide students interested in EM with some resources that can provide them with further guidance to decide whether EM is the right choice for them.

Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma.

Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m2 with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients. During Phase 1, the maximum tolerated dose of POM was 4 mg, and was used in Phase 2, which also required patients to be refractory to LEN. However, neutropenia ≥ grade 3 was observed in 10/17 (59%) patients, and the dose was lowered to 3 mg. Median PFS was 5·4 months (range, 0·3-29·0 +  months). Overall response rates for patients in Phase 2 were 39% and 31% among subjects receiving POM at 3 mg and 4 mg, respectively, and clinical benefit rates were 51% and 44%, respectively. POM, PLD and DEX is a treatment option for relapsed/refractory MM patients including those who are refractory to LEN.

Longitudinal changes in quality of life and rates of progressive visual field loss in glaucoma patients.

PURPOSE: To evaluate the association between longitudinal changes in quality of life (QoL) and rates of progressive visual field loss in glaucoma. DESIGN: Prospective observational cohort study. PARTICIPANTS: We recruited 322 eyes of 161 patients with glaucomatous visual field loss from the Diagnostic Innovations Glaucoma Study followed for an average of 3.5±0.7 years. METHODS: All subjects had National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 performed annually and standard automated perimetry (SAP) at 6-month intervals. Subjects were included if they had a minimum of 2 NEI VFQ-25 and ≥5 SAP during follow-up. Evaluation of rates of visual field change was performed using the mean sensitivity (MS) of the integrated binocular visual field (BVF). Rasch analysis was performed to obtain final scores of disability as measured by the NEI VFQ-25. A joint longitudinal multivariate mixed model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in BVF sensitivity. Potentially confounding socioeconomic and clinical variables also were analyzed. MAIN OUTCOME MEASURES: The relationship between change in NEI VFQ-25 Rasch-calibrated scores and change in binocular SAP MS. RESULTS: There was a significant correlation between change in the NEI VFQ-25 Rasch scores during follow-up and change in binocular SAP sensitivity. Each 1-dB change in binocular SAP MS per year was associated with a change of 2.9 units per year in the NEI VFQ-25 Rasch scores during the follow-up period (R(2) = 26%; P<0.001). Eyes with more severe disease at baseline were also more likely to have a decrease in NEI VFQ-25 scores during follow-up (P<0.001). For subjects with the same amount of change in SAP sensitivity, those with shorter follow-up times had larger changes in NEI VFQ-25 scores (P = 0.005). A multivariable model containing baseline and rate of change in binocular MS had an adjusted R(2) of 50% in predicting change in NEI VFQ-25 scores. CONCLUSIONS: Baseline severity, magnitude, and rates of change in BVF sensitivity were associated with longitudinal changes in QoL of glaucoma patients. Assessment of longitudinal visual field changes may help to identify patients at greater risk for developing disability from the disease.

Simple models to estimate historical and recent changes of total organic carbon concentrations in lakes.

Quantifying human impacts on the natural environment requires credible reconstructions of reference conditions. Anthropogenic acidification of surface waters is strongly influenced by total organic carbon (TOC) concentrations. Because both the degree of acidification and recovery are dependent on historical TOC concentrations, simple models to estimate changes in surface water TOC between reference conditions (1860) and the present day (2012) are needed. We used visible near infrared spectroscopy (VNIRS) of lake sediments to reconstruct reference condition TOC and long-term monitoring data to predict recent changes. Two empirical models were developed to predict: (i) historical TOC trends between reference conditions (1860) and peak acidification (1980) and (ii) trends in TOC between 1988 and 2012. The models were statistically robust with adj. R(2) of (i) 0.85 and (ii) 0.71, respectively. Models were driven by lake and catchment area, wetlands, historical sulfur deposition and water chemistry. Present day TOC concentrations are similar to VNIRS-reconstructed and modeled reference condition TOC in Swedish lakes. The results are valuable for understanding drivers of TOC changes in lakes and for more credible assessments of reference conditions needed for water management in Europe and elsewhere.

A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intolerant to hydroxyurea were studied in a phase 2 trial. METHODS: Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to <45% without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms. RESULTS: Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit <45% without phlebotomy was achieved in 97% of patients by week 24.Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44% and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improvements in pruritus, night sweats, and bone pain were observed within 4 weeks of the initiation of therapy and maintained with continued treatment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events.Thrombocytopenia of grade 3 or anemia of grade 3 (according to National Cancer Institute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) and were managed with dose modification. CONCLUSIONS: Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits in patients with advanced PV who were refractory or intolerant to hydroxyurea.

An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer.

BACKGROUND: Polo-like kinases (Plks) control multiple steps during the cell cycle, and Plk1 is overexpressed in urothelial cancer (UC). Volasertib (BI 6727), a Plk inhibitor, has demonstrated antitumor activity in several malignancies, including UC. In this phase 2 trial, the authors investigated volasertib as a second-line treatment in advanced/metastatic UC. METHODS: Patients who progressed within 2 years of 1 prior chemotherapy regimen received 300 mg volasertib on day 1 every 3 weeks. The dose was escalated to 350 mg in cycle 2 if volasertib was tolerated in cycle 1. The primary endpoint was tumor response, which was assessed every 6 weeks; secondary endpoints were progression-free survival, overall survival, duration of response, safety, and pharmacokinetics. RESULTS: Fifty patients were enrolled, and the median patient age was 68.5 years (range, 52-83 years). All patients had received prior platinum, 94% of patients had relapsed ≤2 years after prior therapy, 36% had liver metastases, and 54% had lung metastases. The median number of treatment cycles was 2 (range, 1-27 treatment cycles), and 23 patients were dose escalated at cycle 2. Seven patients (14%) had a partial response, 13 (26%) had stable disease, and 30 (60%) progressed within 6 weeks. The median response duration was 41 weeks (range, 29.1-77.3 weeks). The median progression-free survival was 1.4 months, and the median overall survival was 8.5 months. The most frequent grade 3 and 4 adverse events were neutropenia (28%), thrombocytopenia (20%), and anemia (16%). No cumulative toxicity was observed. CONCLUSIONS: Volasertib as second-line treatment for advanced/metastatic UC had an acceptable safety profile but demonstrated insufficient antitumor activity for further evaluation as a monotherapy.

An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma.

Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m(2) for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m(2) for cycle 1 and then 27 mg/m(2) for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy-17.1% overall (1 grade 3; no grade 4)-in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.

Disseminated intravascular coagulation secondary to advanced pancreatic cancer treated successfully with combination chemotherapy.

Both solid and hematologic malignancies may be complicated by coagulopathies. Disseminated intravascular coagulation (DIC) in the presence of pancreatic cancer is generally unrecognized and may have fatal consequences. The diagnosis of DIC in a patient with advanced cancer is a poor prognostic indicator. Presented here is a case study consisting of two patients presenting with a new diagnosis of pancreatic cancer complicated by DIC. Aggressive supportive treatment in addition to systemic chemotherapy consisting of gemcitabine and nab-paclitaxel was initiated and DIC was controlled. An early diagnosis of DIC and the administration of systemic chemotherapy with a high response rate and an ability to reduce tumor bulk rapidly may offer some patients the probability of recovery.

Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma.

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m² (n = 2) or 120 mg/m² (n = 57) on days 1 and 2 and rituximab at 375 mg/m² on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile.

Staff pooling in healthcare systems - results from a mixed-methods study.

This study examines how staff pooling can be used to create a higher service level at a predetermined total capacity in the healthcare sector. We develop new empirical knowledge through a systematic empirical study, using a mixed-methods approach, with a preliminary interview study followed by a principal quantitative survey study, with data from a multihospital system. The purpose was to explore practical barriers for a staff pooling strategy in healthcare systems. Three barriers were identified:recruitment difficulties, community view, and specialisation. Significant differences in perceived height among these barriers were found. The results from this study have important managerial implications for healthcare systems when implementing a staff pooling approach. This study contributes to the existing literature since, to the best of our knowledge, no previous research has been done where barriers to staff pools are systematically identified using a holistic approach that includes all healthcare professions in a multihospital system.

DUAL ACTION ELECTROCHEMICAL BANDAGE OPERATED by a PROGRAMMABLE MULTIMODAL WEARABLE POTENTIOSTAT.

Electrochemical bandages (e-bandages) can be applied to biofilm-infected wounds to generate reactive oxygen species, such as hypochlorous acid (HOCl) or hydrogen peroxide (H 2 O 2 ). The e-bandage-generated HOCl or H 2 O 2 kills biofilms in vitro and in infected wounds on mice. The HOCl-generating e-bandage is more active against biofilms in vitro , although this distinction is less apparent in vivo . The H 2 O 2 -generating e-bandage, more than the HOCl-generating e-bandage, is associated with improved healing of infected wounds. A strategy in which H 2 O 2 and HOCl are generated alternately-for dual action-was explored. The goal was to develop a programmable multimodal wearable potentiostat (PMWP) that could be programmed to generate HOCl or H 2 O 2 , as needed. An ultralow-power microcontroller unit managed operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 grams, making it suitable for small animal experiments or human use. The overall cost of a single wearable potentiostat was $6.50 (USD). The device was verified using established electrochemical systems and functioned comparably to a commercial potentiostat. To determine antimicrobial effectiveness, PMWP-controlled e-bandages were tested against clinical isolates of four prevalent chronic wound bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii , and Enterococcus faecium , and one fungal pathogen of emerging concern, Candida auris . PMWP-controlled e-bandages exhibited broad-spectrum activity against biofilms of all study isolates tested when programmed to deliver HOCl followed by H 2 O 2 . These results show that the PMWP operates effectively and is suitable for animal testing.

United States version of the Stroke Driver Screening Assessment: a pilot study.

BACKGROUND: Most stroke survivors who resume driving in the United States do so within the first year. More than 87% of these individuals resume driving without a formal evaluation of their fitness to drive because of the absence of standard practices and generally accepted and valid screening tools. The Stroke Driver Screening Assessment (SDSA) is an established battery for predicting stroke survivors' driving performance but is not currently used in the United States. This pilot study investigated the predictive ability of the US version of the battery in a US-based cohort of stroke survivors. METHOD: Fifteen first-ever stroke survivors (age, 52±12 years) and 16 healthy adults (age, 40±16 years) were administered the US version of the SDSA in a standardized format. Performance on the SDSA was compared with driving performance in a high-fidelity driving simulator. RESULTS: Stroke and healthy participants' driving performance was predicted with 87% and 88% accuracy, respectively. CONCLUSION: The US version of the SDSA battery has the potential to be a good predictor of driving performance of mildly impaired stroke survivors. Larger studies are needed to further establish its predictive accuracy.

Alterations in error-related brain activity and post-error behavior over time.

This study examines the relation between the error-related negativity (ERN) and post-error behavior over time in healthy young adults (N=61). Event-related brain potentials were collected during two sessions of an identical flanker task. Results indicated changes in ERN and post-error accuracy were related across task sessions, with more negative ERN associated with greater improvements in post-error accuracy. This relationship was independent of any cross-sectional relationships between overall task performance, individual difference factors, including personality and self-efficacy, and indices of self-regulatory action monitoring. These results indicate that the relation between ERN and post-error accuracy remains intact and consistent regardless of variation in this set of individual difference factors previously associated with both of these indices of self-regulatory action monitoring, providing support for the strength, robustness, and persistence of this relationship in the process of adaptively controlling behavior to enhance task performance.

Brain natriuretic peptide in the evaluation of emergency department dyspnea: is there a role?

BACKGROUND: Acute decompensated congestive heart failure (ADCHF) is a common etiology of dyspnea in emergency department (ED) patients. Delayed diagnosis of ADCHF increases morbidity and mortality. Two cardiac biomarkers, N-terminal-pro brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) have demonstrated excellent sensitivity in diagnostic accuracy studies, but the clinical impact on patient-oriented outcomes of these tests remains in question. CLINICAL QUESTION: Does emergency physician awareness of BNP or NT-proBNP level improve ADCHF patient-important outcomes including ED length of stay, hospital length of stay, cardiovascular mortality, or overall health care costs? EVIDENCE REVIEW: Five trials have randomized clinicians to either knowledge of or no knowledge of ADCHF biomarker levels in ED patients with dyspnea and some suspicion for heart failure. In assessing patient-oriented outcomes such as length-of-stay, return visits, and overall health care costs, the randomized controlled trials fail to provide evidence of unequivocal benefit to patients, clinicians, or society. CONCLUSION: Clinician awareness of BNP or NT-proBNP levels in ED dyspnea patients does not necessarily improve outcomes. Future ADCHF biomarker trials must assess patient-oriented outcomes in conjunction with validated risk-stratification instruments.

Driving simulation for evaluation and rehabilitation of driving after stroke.

Driving is an important activity of daily living. Loss of driving privileges can lead to depression, decreased access to medical care, and increased healthcare costs. The ability to drive is often affected after stroke. In approximately 30% of stroke survivors, it is clear from the onset that driving will no longer be possible. Approximately 33% of survivors will be able to return to driving with little or no retraining, and 35% will require driving-related rehabilitation before they can resume safe driving again. The ability to drive is not routinely evaluated after stroke, and there is no established rehabilitation program for poststroke driving. When driving evaluation does occur, it is not always clear which tests are the most salient for accurately assessing poststroke driving ability. Investigators have examined the efficacy of various methodologies to predict driving performance after stroke and have found mixed results, with each method having unique weaknesses, including poor predictive ability, poor face validity, poor sensitivity or specificity, and limited reliability. Here we review common models of driving to gain insight into why single-construct visual or cognitive off-road measures are inadequate for evaluating driving, a complex and dynamic activity that involves timely interaction of multiple motor, visual, cognitive, and perceptual skills. We also examine the potential for driving simulators to overcome the problems currently faced in the evaluation and rehabilitation of driving after stroke. Finally, we offer suggestions for the future direction of simulator-based poststroke driving evaluation and training.

Hospital Staffing during the COVID-19 Pandemic in Sweden.

Staff management challenges in the healthcare system are inherently different during pandemic conditions than under normal circumstances. Surge capacity must be rapidly increased, particularly in the intensive care units (ICU), to handle the increased pressure, without depleting the rest of the system. In addition, sickness or fatigue among the staff can become a critical issue. This study explores the lessons learned by first- and second-line managers in Sweden with regard to staff management during the COVID-19 pandemic. A mixed-methods approach was used, with preliminary qualitative interview (n = 38) and principal quantitative questionnaire (n = 272) studies, based on principal component and multiple regression analyses. The results revealed that the pandemic created four types of challenges relating to staff management: staff movement within hospitals; addition of external staff; addition of hours for existing staff through overtime and new shift schedules; and avoidance of lost hours due to sickness or fatigue. Furthermore, the effects of these managerial challenges were different in the first wave than in later waves, and they significantly differed between the ICU and other units. Therefore, a greater proactive focus on staff management would be beneficial in future pandemic situations.

Universally applicable model for the quantitative determination of lake sediment composition using fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FTIRS) can provide detailed information on organic and minerogenic constituents of sediment records. Based on a large number of sediment samples of varying age (0-340,000 yrs) and from very diverse lake settings in Antarctica, Argentina, Canada, Macedonia/Albania, Siberia, and Sweden, we have developed universally applicable calibration models for the quantitative determination of biogenic silica (BSi; n = 816), total inorganic carbon (TIC; n = 879), and total organic carbon (TOC; n = 3164) using FTIRS. These models are based on the differential absorbance of infrared radiation at specific wavelengths with varying concentrations of individual parameters, due to molecular vibrations associated with each parameter. The calibration models have low prediction errors and the predicted values are highly correlated with conventionally measured values (R = 0.94-0.99). Robustness tests indicate the accuracy of the newly developed FTIRS calibration models is similar to that of conventional geochemical analyses. Consequently FTIRS offers a useful and rapid alternative to conventional analyses for the quantitative determination of BSi, TIC, and TOC. The rapidity, cost-effectiveness, and small sample size required enables FTIRS determination of geochemical properties to be undertaken at higher resolutions than would otherwise be possible with the same resource allocation, thus providing crucial sedimentological information for climatic and environmental reconstructions.