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Background: Persistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS.Objective/Hypothesis: We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.e., left dorsolateral prefrontal cortex (DLPFC) compared to control tDCS.Methods: Thirty-four subjects with mmTBI underwent baseline assessments of demographics, symptoms, and cognitive function as well as resting state functional magnetic resonance imaging (rsfMRI) in a subset of patients (n = 24). Primary outcome measures included NIH EXAMINER composite scores, and the Neurobehavioral Symptom Inventory (NSI). All participants received 10 daily sessions of 30 min of executive function training coupled with active or control tDCS (2 mA, anode F3, cathode right deltoid). Imaging and assessments were re-obtained after the final training session, and assessments were repeated after 1 month. Mixed-models linear regression and repeated measures analyses of variance were calculated for main effects and interactions.Results: Both active and control groups demonstrated improvements in executive function (EXAMINER composite: p < 0.001) and posttraumatic symptoms (NSI cognitive: p = 0.01) from baseline to 1 month. Active anodal tDCS was associated with greater improvements in working memory reaction time compared to control (p = 0.007). Reaction time improvement correlated significantly with the degree of connectivity change between the right DLPFC and the left anterior insula (p = 0.02).Conclusion: Anodal tDCS improved reaction time on an online working memory task in a mmTBI population, and decreased connectivity between executive network and salience network nodes. These findings generate important hypotheses for the mechanism of recovery from PPS after mild-moderate TBI.

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis.MethodsWe characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronic-bronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort.ResultsMean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 μg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 μg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort.ConclusionsAirway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.).

ImportanceThe notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s.ObjectiveTo evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy.Evidence reviewA panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained.FindingsThirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment.Conclusions and relevancePhysicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.

We have verified a mechanism for Raman excitation of atoms through continuum levels previously obtained by quantum optimal control using the multiconfigurational time-dependent Hartree-Fock (MCTDHF) method. For the optimal control, which requires running multiple propagations to determine the optimal pulse sequence, we used the computationally inexpensive time-dependent configuration interaction singles (TDCIS) method. TDCIS captures all of the necessary correlation of the desired processes but assumes that ionization pathways reached via double excitations are not present. MCTDHF includes these pathways and all multiparticle correlations in a set of time-dependent orbitals. The mechanism that was determined to be optimal in the Raman excitation of the Ne 1s22s22p53p1 valence state via the metastable 1s22s12p63p1 resonance state involves a sequential resonance-valence excitation. First, a long pump pulse excites the core-hole state, and then a shorter Stokes pulse transfers the population to the valence state. This process represents the first step in a multidimensional x-ray spectroscopy scheme that will provide a local probe of valence electronic correlations. Although at the optimal pulse intensities at the TDCIS level of theory the MCTDHF method predicts multiple ionization or excitation ionization of the atom, at slightly lower intensities (reduced by a factor of about 4) the TDCIS mechanism is shown to hold qualitatively. Quantitatively, the MCTDHF populations are reduced from the TDCIS calculations by a factor of 4.

The method of complex basis functions is applied to molecular resonances at correlated levels of theory. Møller-Plesset perturbation theory at second order and equation-of-motion electron attachment coupled-cluster singles and doubles (EOM-EA-CCSD) methods based on a non-Hermitian self-consistent-field reference are used to compute accurate Siegert energies for shape resonances in small molecules including N2-, CO-, CO2-, and CH2O-. Analytic continuation of complex ?-trajectories is used to compute Siegert energies, and the ?-trajectories of energy differences are found to yield more consistent results than those of total energies. The ability of such methods to accurately compute complex potential energy surfaces is investigated, and the possibility of using EOM-EA-CCSD for Feshbach resonances is explored in the context of e-helium scattering.

We used extreme ultraviolet (XUV) transient absorption spectroscopy to study the autoionizing Rydberg states of oxygen in an electronically- and vibrationally-resolved fashion. XUV pulse initiates molecular polarization and near-infrared pulse perturbs its evolution. Transient absorption spectra show positive optical-density (OD) change in the case of nsσg and ndπg autoionizing states of oxygen and negative OD change for ndσg states. Multiconfiguration time-dependent Hartree-Fock (MCTDHF) calculations are used to simulate the transient absorption and the resulting spectra and temporal evolution agree with experimental observations. We model the effect of near-infrared perturbation on molecular polarization and find that the laser-induced phase-shift model agrees with the experimental and MCTDHF results, while the laser-induced attenuation model does not. We relate the electronic-state-symmetry-dependent sign of the OD change to the Fano parameters of the static absorption line shapes.

The computation of Siegert energies by analytic continuation of bound state energies has recently been applied to shape resonances in polyatomic molecules by several authors. We critically evaluate a recently proposed analytic continuation method based on low order (type III) Padé approximants as well as an analytic continuation method based on high order (type II) Padé approximants. We compare three classes of stabilizing potentials: Coulomb potentials, Gaussian potentials, and attenuated Coulomb potentials. These methods are applied to a model potential where the correct answer is known exactly and to the Πg2 shape resonance of N2- which has been studied extensively by other methods. Both the choice of stabilizing potential and method of analytic continuation prove to be important to the accuracy of the results. We conclude that an attenuated Coulomb potential is the most effective of the three for bound state analytic continuation methods. With the proper potential, such methods show promise for algorithmic determination of the positions and widths of molecular shape resonances.

BackgroundOur study addresses the gaps in knowledge of the characterizations of operations by remote tele-critical care medicine (tele-CCM) service providers interacting with the bedside team. The duration of engagements, the evolution of the tele-CCM service over time, and the distress during interactions with the bedside team have not been characterized systematically. These characteristics are critical for planning the deployment of teleICU services and preventing burnout among remote teleICU providers.MethodsREDCap self-reported activity logs collected engagement duration, triggers (emergency button, tele-CCM software platform, autonomous algorithm, asymmetrical communication platform, phone), expediency, nature (proactive rounding, predetermined task, response to medical needs), communication modes, and acceptance. Seven hospitals with 16 ICUs were overseen between 9/2020 and 9/2021 by teams consisting of telemedicine medical doctors (eMD), telemedicine registered nurses (eRN), and telemedicine respiratory therapists (eRT).Results39,915 total engagements were registered. eMDs had a significantly higher percentage of emergent and urgent engagements (31.9%) vs. eRN (9.8%) or eRT (1.7%). The average tele-CCM intervention took 16.1 ± 10.39 min for eMD, 18.1 ± 16.23 for eRN, and 8.2 ± 4.98 min for eRT, significantly varied between engagement, and expediency, hospitals, and ICUs types. During the observation period, there was a shift in intervention triggers with an increase in autonomous algorithmic ARDS detection concomitant with predominant utilization of asynchronous communication, phone engagements, and the tele-CCM module of electronic medical records at the expense of the share of proactive rounding. eRT communicated more frequently with bedside staff (% MD = 37.8%; % RN = 36.8, % RT = 49.0%) but mostly with other eRTs. In contrast, the eMD communicated with all ICU stakeholders while the eRN communicated chiefly with other RN and house staff at the patient's bedside. The rate of distress reported by tele-CCM staff was 2% among all interactions, with the entity hospital being the dominant factor.ConclusionsDelivery of tele-CCM services has to be tailored to the specific beneficiary of tele-CCM services to optimize care delivery and minimize distress. In addition, the duration of the average intervention must be considered while creating an efficient workflow.

Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high‐risk medications in patients at risk of TdP, but alerts are often ignored. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class (P

Abstract Antiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular ‘Works in Progress’ meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor–mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.

: Introduction: Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID‐19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. Methods: From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence ( Results: Questions about pandemic‐related consequences for HIV care were completed by 225 (95%) sites in 42 countries with low (n = 82), medium (n = 86) and high (n = 57) HIV prevalence, including low‐ (n = 57), lower‐middle (n = 79), upper‐middle (n = 39) and high‐ (n = 50) income countries. Most sites reported being subject to pandemic‐related restrictions on travel, service provision or other operations (75%), and experiencing negative impacts (76%) on clinic operations, including decreased hours/days, reduced provider availability, clinic reconfiguration for COVID‐19 services, record‐keeping interruptions and suspension of partner support. Almost all sites in low‐prevalence and high‐income countries reported increased use of telemedicine (85% and 100%, respectively), compared with less than half of sites in high‐prevalence and lower‐income settings. Few sites in high‐prevalence settings (2%) reported suspending antiretroviral therapy (ART) clinic services, and many reported adopting mitigation strategies to support adherence, including multi‐month dispensing of ART (95%) and designating community ART pick‐up points (44%). While few sites (5%) reported stockouts of first‐line ART regimens, 10–11% reported stockouts of second‐ and third‐line regimens, respectively, primarily in high‐prevalence and lower‐income settings. Interruptions in HIV viral load (VL) testing included suspension of testing (22%), longer turnaround times (41%) and supply/reagent stockouts (22%), but did not differ across settings. Conclusions: While many sites in high HIV prevalence settings and lower‐income countries reported introducing or expanding measures to support treatment adherence and continuity of care, the COVID‐19 pandemic resulted in disruptions to VL testing and ART supply chains that may negatively affect the quality of HIV care in these settings., INTRODUCTION The COVID‐19 pandemic has had major direct and indirect impacts on population health globally, through disruptions in the accessibility and quality of basic health services [1], in supply chains [...]

Cerebral autoregulation is an intrinsic myogenic response of cerebral vasculature that allows for preservation of stable cerebral blood flow levels in response to changing systemic blood pressure. It is effective across a broad range of blood pressure levels through precapillary vasoconstriction and dilation. Autoregulation is difficult to directly measure and methods to indirectly ascertain cerebral autoregulation status inherently require certain assumptions. Patients with impaired cerebral autoregulation may be at risk of brain ischemia. One of the central mechanisms of ischemia in patients with metabolically compromised states is likely the triggering of spreading depolarization (SD) events and ultimately, terminal (or anoxic) depolarization. Cerebral autoregulation and SD are therefore linked when considering the risk of ischemia. In this scoping review, we will discuss the range of methods to measure cerebral autoregulation, their theoretical strengths and weaknesses, and the available clinical evidence to support their utility. We will then discuss the emerging link between impaired cerebral autoregulation and the occurrence of SD events. Such an approach offers the opportunity to better understand an individual patient's physiology and provide targeted treatments. [ABSTRACT FROM AUTHOR]

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Background: Blood pressure (BP) is routinely invasively monitored by an arterial catheter in the intensive care unit (ICU). However, the available data comparing the accuracy of noninvasive methods to arterial catheters for measuring BP in the ICU are limited by small numbers and diverse methodologies. Purpose: To determine agreement between invasive arterial blood pressure monitoring (IABP) and noninvasive blood pressure (NIBP) in critically ill patients. Methods: This was a single center, observational study of critical ill adults in a tertiary care facility evaluating agreement (≤10% difference) between simultaneously measured IABP and NIBP. We measured clinical features at time of BP measurement inclusive of patient demographics, laboratory data, severity of illness, specific interventions (mechanical ventilation and dialysis), and vasopressor dose to identify particular clinical scenarios in which measurement agreement is more or less likely. Results: Of the 1852 critically ill adults with simultaneous IABP and NIBP readings, there was a median difference of 6 mm Hg in mean arterial pressure (MAP), interquartile range (1-12), P <.01. A logistic regression analysis identified 5 independent predictors of measurement discrepancy: increasing doses of norepinephrine (adjusted odds ratio [aOR] 1.10 [95% confidence interval, CI 1.08-1.12] P =.03 for every change in 5 µg/min), lower MAP value (aOR 0.98 [0.98-0.99] P <.01 for every change in 1 mm Hg), higher body mass index (aOR 1.04 [1.01-1.09] P =.01 for an increase in 1), increased patient age (aOR 1.31 [1.30-1.37] P <.01 for every 10 years), and radial arterial line location (aOR 1.74 [1.16-2.47] P =.04). Conclusions: There was broad agreement between IABP and NIBP in critically ill patients over a range of BPs and severity of illness. Several variables are associated with measurement discrepancy; however, their predictive capacity is modest. This may guide future study into which patients may specifically benefit from an arterial catheter. [ABSTRACT FROM AUTHOR]

Background: In 2021, Mozambique initiated community-based oral HIV self-testing (HIVST) to increase testing access and uptake among priority groups, including adult males, adolescents, and young adults. Within an HIVST pilot project, we conducted a performance evaluation assessing participants' ability to successfully conduct HIVST procedures and interpret results. Methods: A cross-sectional study was performed between February-March 2021 among employees, students (18–24 years of age), and community members, using convenience sampling, in two rural districts of Zambézia Province, Mozambique. We quantified how well untrained users performed procedures for the oral HIVST (Oraquick®) through direct observation using a structured checklist, from which we calculated an HIVST usability index (scores ranging 0–100%). Additionally, participants interpreted three previously processed anonymous HIVST results. False reactive and false non-reactive interpretation results were presented as proportions. Bivariate analysis was conducted using Chi-square and Fisher exact tests. Results: A total of 312 persons participated (131[42%] community members, 71[23%] students, 110[35%] employees); 239 (77%) were male; the mean age was 28 years (standard deviation 10). Average usability index scores were 80% among employees, 86% among students, and 77% among community members. Main procedural errors observed included "incorrect tube positioning" (49%), "incorrect specimen collection" (43%), and "improper waiting time for result interpretation" (42%). From the presented anonymous HIVST results, 75% (n = 234) correctly interpreted all three results, while 9 (3%) of study participants failed to correctly interpret any results. Overall, 36 (12%) gave a false non-reactive result interpretation, 21 (7%) a false reactive result interpretation, and 14 (4%) gave both false non-reactive and false reactive result interpretations. Community members generally had lower performance. Conclusions: Despite some observed testing procedural errors, most users could successfully perform an HIVST. Educational sessions at strategic places (e.g., schools, workplaces), and support via social media and hotlines, may improve HIVST performance quality, reducing the risk of incorrect interpretation. [ABSTRACT FROM AUTHOR]

The monogeneric family Calomyscidae includes the brush-tailed mice, genus Calomyscus , which have a Palearctic distribution ranging from the Hindu Kush Mountains in western Pakistan to the eastern Mediterranean region. Zagros Mountains—stretching from northwest to south of Iran—was assumed for long as the range of a single species, Calomyscus bailwardi ; however, recent studies revealed considerable heterogeneities among the geographical populations presumably referring to the persistence of undescribed diversity. One such group from the western Zagros Mountains has recently been recognized as C. behzadi Akbarirad, Dezhman, Aliabadian, Siahsarvie, Shafaeipour, and Mirshamsi, 2021. Using molecular, morphometric, geometric morphometric, and karyotypic data, we examine the divergence of 2 additional groups from western Iran and name these as new species. The first of these species is distributed in the northern Zagros and western Alborz Mountains in northwestern Iran was recovered as the sister species to C. urartensis from the South Caucuses. The second species from a single locality in the central Zagros Mountains was clustered closely with C. grandis from the western Alborz Mountains. Morphologic analyses, karyological features, and genetic distances disentangled these 2 new species from their sister species. [ABSTRACT FROM AUTHOR]

ABSTRACT The emergence of biofilms on dry hospital surfaces has led to the development of numerous models designed to challenge the efficacious properties of common antimicrobial agents used in cleaning. This is in spite of limited research defining how dry surfaces are able to facilitate biofilm growth and formation in such desiccating and nutrient-deprived environments. While it is well established that the phenotypical response of biofilms is dependent on the conditions in which they are formed, most models incorporate a nutrient-enriched, hydrated environment dissimilar to the clinical setting. In this study, we piloted a novel culture medium, artificial human sweat (AHS), which is perceived to be more indicative of the nutrient sources available on hospital surfaces, particularly those in close proximity to patients. AHS was capable of sustaining the proliferation of four clinically relevant multidrug-resistant pathogens (Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa) and achieved biofilm formation at concentration levels equivalent to those found in situ (average, 6.00 log10 CFU/cm2) with similar visual characteristics upon microscopy. The AHS model presented here could be used for downstream applications, including efficacy testing of hospital cleaning products, due to its resemblance to clinical biofilms on dry surfaces. This may contribute to a better understanding of the true impact these products have on surface hygiene. IMPORTANCE Precise modeling of dry surface biofilms in hospitals is critical for understanding their role in hospital-acquired infection transmission and surface contamination. Using a representative culture condition which includes a nutrient source is key to developing a phenotypically accurate biofilm community. This will enable accurate laboratory testing of cleaning products and their efficacy against dry surface biofilms.