An examination of housing interventions among youth experiencing homelessness: an investigation into racial/ethnic and sexual minority status.

OBJECTIVES: The purpose of this study is to explore main and interaction effects of minority and multiple minority statuses on exits from homelessness and the stability of homelessness exits overtime. METHODS: This study utilized the Homeless Management Information System administrative data of 10 922 youth experiencing homelessness collected from a convenience sample of 16 geographically diverse communities across the USA between 2015-17. Using multinomial logistic regression analyses and logistic regression, main effects and interaction effects of racial/ethnic minority identity and sexual/gender minority identity were examined on various homelessness exits (n = 9957) and housing sustainability (n = 5836). RESULTS: Black youth, relative to White youth, were disproportionately exiting homelessness through incarceration (P < 0.001). Black and Latinx youth were less likely to successfully self-resolve their homelessness (both P < 0.05). Black heterosexual and Black and Latinx non-heterosexual youth were most frequently lost to the homeless system (all P < 0.01). Black youth, relative to White youth, were approximately half as likely to remain stably housed after returning to family (P < 0.01). CONCLUSIONS: With respect to housing exits and exit stability, Black and Latinx heterosexual youth are consistently at a disadvantage. Homelessness/housing systems and programs need to conduct a deeper investigation into how they implement and develop equitable outreach and engagement practices.

Hospital-Based Suicides: Challenging Existing Myths.

Myths are widely held and often based on false beliefs. To improve patient safety and speed the translation of research to clinical practice, we highlight and then debunk 10 common myths regarding the assessment, treatment, and management of hospitalized patients at risk for suicide. Myths regarding hospital-based suicides are examined and empirical evidence that counters each myth is offered. Ten common myths regarding hospital-based suicides are found to be untrue or unsupported based on existing empirical evidence. Rethinking common beliefs and practices that lack empirical support and seeking alternatives based on research evidence is consistent with an emphasis on evidence-based practices leading to improved patient care and protection.

The effect of anodal/cathodal biphasic electrical stimulation on insulin release.

We studied the effects of electrical stimulation on insulin release from rat insulinoma (INS-1) cells. The anodal/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage- and stimulation duration-dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Basal and ACBPS-induced insulin secretion could be inhibited by mitochondrial poisons and calcium channel blockers, indicating that insulin release was dependent on adenosine triphosphate (ATP) and the influx of calcium. ACBPS parameters that released insulin caused no detectable plasma membrane damage or cytotoxicity, although temporary morphological changes could be observed immediately after ACBPS. ACBPS did not alter the plasma membrane transmembrane potential but did cause pronounced uptake of MitoTracker Red into the mitochondrial membrane, indicating an increased mitochondrial membrane potential. While the ATP:ADP ratio after ACBPS did not change, the guanosine triphosphate (GTP) levels increased and increased GTP levels have previously been associated with insulin release in INS-1 cells. These results provide evidence that ACBPS can have significant biological effects on cells. In the case of INS-1 cells, ACBPS promotes insulin release without causing cytotoxicity.

From Yielding to Shear Jamming in a Cohesive Frictional Suspension.

Simulations are used to study the steady shear rheology of dense suspensions of frictional particles exhibiting discontinuous shear thickening and shear jamming, in which finite-range cohesive interactions result in a yield stress. We develop a constitutive model that combines yielding behavior and shear thinning at low stress with the frictional shear thickening at high stresses, in good agreement with the simulation results. This work shows that there is a distinct difference between solids below the yield stress and in the shear-jammed state, as the two occur at widely separated stress levels, with an intermediate region of stress in which the material is flowable.

Effects of biphasic and monophasic electrical stimulation on mitochondrial dynamics, cell apoptosis, and cell proliferation.

Currently, electrical stimulation (ES) is used to induce changes in various tissues and cellular processes, but its effects on mitochondrial dynamics and mechanisms are unknown. The aim of this study was to compare the effects of monophasic and biphasic, anodal, and cathodal ES on apoptosis, proliferation, and mitochondrial dynamics in neuroblastoma SH-SY5Y cells. Cells were cultured and treated with ES. Alamar blue assay was performed to measure cell proliferation. The proteins expression of apoptotic-related proteins Bcl-2 associated X (Bax), B cell lymphoma 2 (Bcl-2), optic-atrophy-1 (OPA1), mitofusin2 (Mfn2), phosphorylated dynamin-related protein 1 at serine 616 (p-DRP1), and total dynamin-related protein 1 (Total-DRP1) were also determined. The results showed that monophasic anodal and biphasic anodal/cathodal (Bi Anod) ES for 1 hr at 125 pulses per minute (2.0 Hz) produced the most significant increase in cell proliferation. In addition, monophasic anodal and Bi Anod ES treated cells displayed a significant increase in the levels of anti-apoptotic protein Bcl-2, whereas the Bax levels were not changed. Moreover, the levels of Mfn2 were increased in the cells treated by Bi Anod, and OPA1 was increased by monophasic anodal and Bi Anod ES, indicating increased mitochondrial fusion in these ES-treated cells. However, the levels of mitochondrial fission indicated by DRP1 remained unchanged compared with non-stimulated cells. These findings were confirmed through visualization of mitochondria using Mitotracker Deep Red, demonstrating that monophasic anodal and Bi Anod ES could induce pro-survival effects in SH-SY5Y cells through increasing cell proliferation and mitochondrial fusion. Future research is needed to validate these findings for the clinical application of monophasic anodal and Bi Anod ES.

Shear thickening in concentrated suspensions of smooth spheres in Newtonian suspending fluids.

Shear thickening is a phenomenon in which the viscosity of a suspension increases with increasing stress or shear rate, sometimes in a discontinuous fashion. While the phenomenon, when observed in suspensions of corn starch in water, or Oobleck, is popular as a science experiment for children, shear thickening is actually of considerable importance for technological applications and exhibited by far simpler systems. Concentrated suspensions of smooth hard spheres will exhibit shear thickening, and understanding this behavior has required a fundamental change in the paradigm of describing low-Reynolds-number solid-fluid flows, in which contact forces have traditionally been absent. Here, we provide an overview of our understanding of shear thickening and the methods that have been developed to describe it, as well as outstanding questions.

Discontinuous shear thickening in Brownian suspensions by dynamic simulation.

Dynamic particle-scale numerical simulations are used to show that the shear thickening observed in dense colloidal, or Brownian, suspensions is of a similar nature to that observed in noncolloidal suspensions, i.e., a stress-induced transition from a flow of lubricated near-contacting particles to a flow of a frictionally contacting network of particles. Abrupt (or discontinuous) shear thickening is found to be a geometric rather than hydrodynamic phenomenon; it stems from the strong sensitivity of the jamming volume fraction to the nature of contact forces between suspended particles. The thickening obtained in a colloidal suspension of purely hard frictional spheres is qualitatively similar to experimental observations. However, the agreement cannot be made quantitative with only hydrodynamics, frictional contacts, and Brownian forces. Therefore, the role of a short-range repulsive potential mimicking the stabilization of actual suspensions on the thickening is studied. The effects of Brownian and repulsive forces on the onset stress can be combined in an additive manner. The simulations including Brownian and stabilizing forces show excellent agreement with experimental data for the viscosity η and the second normal stress difference N2.

Reformulating Suicide Risk Formulation: From Prediction to Prevention.

Psychiatrists-in-training typically learn that assessments of suicide risk should culminate in a probability judgment expressed as "low," "moderate," or "high." This way of formulating risk has predominated in psychiatric education and practice, despite little evidence for its validity, reliability, or utility. We present a model for teaching and communicating suicide risk assessments without categorical predictions. Instead, we propose risk formulations which synthesize data into four distinct judgments to directly inform intervention plans: (1) risk status (the patient's risk relative to a specified subpopulation), (2) risk state (the patient's risk compared to baseline or other specified time points), (3) available resources from which the patient can draw in crisis, and (4) foreseeable changes that may exacerbate risk. An example case illustrates the conceptual shift from a predictive to a preventive formulation, and we outline steps taken to implement the model in an academic psychiatry setting. Our goal is to inform educational leaders, as well as individual educators, who can together cast a prevention-oriented vision in their academic programs.

Epstein-Barr virus infection in adult renal transplant recipients.

Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p = 0.045), non-White ethnicity (p = 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p = 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p = 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays.

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies - radioligand-binding or automated electrophysiology - was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost.

Training for suicide risk assessment and suicide risk formulation.

Suicide and suicidal behaviors are highly associated with psychiatric disorders. Psychiatrists have significant opportunities to identify at-risk individuals and offer treatment to reduce that risk. Although a suicide risk assessment (SRA) is a core competency requirement, many lack the requisite training and skills to appropriately assess for suicide risk. Moreover, the standard of care requires psychiatrists to foresee the possibility that a patient might engage in suicidal behavior, hence to conduct a suicide risk formulation (SRF) sufficient to guide triage and treatment planning. An SRA gathers data about observable and reported symptoms, behaviors, and historical factors that are associated with suicide risk and protection, ascertained by way of psychiatric interview; collateral information from family, friends, and medical records; and psychometric scales and/or screening tools. Based on data collected via an SRA, an SRF is a process whereby the psychiatrist forms a judgment about a patient's foreseeable risk of suicidal behavior in order to inform triage decisions, safety and treatment plans, and interventions to reduce risk. This paper addresses the need for a revised training model in SRA and SRF, and proposes a model of training that incorporates the acquisition of skills, relying heavily on case application exercises.

Discontinuous shear thickening of frictional hard-sphere suspensions.

Discontinuous shear thickening (DST) observed in many dense athermal suspensions has proven difficult to understand and to reproduce by numerical simulation. By introducing a numerical scheme including both relevant hydrodynamic interactions and granularlike contacts, we show that contact friction is essential for having DST. Above a critical volume fraction, we observe the existence of two states: a low viscosity, contactless (hence, frictionless) state, and a high viscosity frictional shear jammed state. These two states are separated by a critical shear stress, associated with a critical shear rate where DST occurs. The shear jammed state is reminiscent of the jamming phase of granular matter. Continuous shear thickening is seen as a lower volume fraction vestige of the jamming transition.

Validation of an in vitro contractility assay using canine ventricular myocytes.

Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ~36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration-effect curves were constructed for each compound in 4-30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6-8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds.

Atrial burst pacing with biphasic and monophasic waveforms for atrial fibrillation.

BACKGROUND: Biphasic pacing is a novel mode of pacing that was suggested to increase cardiac conduction velocity as compared with cathodal monophasic pacing. We aimed to evaluate the safety and efficacy of rapid atrial pacing to convert atrial fibrillation (AF) to normal sinus rhythm. METHODS: Multiple biphasic (anodal/cathodal), reverse biphasic (cathodal/anodal), and monophasic (cathodal) atrial pacing therapies were performed among 12 patients undergoing left atrial catheter ablation for AF. The efficacy end point was successful conversion of AF to sinus rhythm, and safety end point no induction of ventricular arrhythmias. Patients were paced at three cycle lengths (100, 200, and 333 msec) for 60 seconds at three locations (right and left atrial appendages and coronary sinus). RESULTS: Among the 66 biphasic (anodal/cathodal) pacing procedures one procedure in a patient with chronic AF, which involved pacing at the left atrial appendage with a cycle length of 200 msec, led to conversion of AF to sinus rhythm. None of the 66 monophasic pacing procedures or the 66 reverse biphasic (cathodal/anodal) pacing procedures was associated with AF termination. None of the biphasic pacing procedures was associated with induction of ventricular arrhythmias. CONCLUSIONS: Rapid atrial pacing using a variety of waveforms at the cycle length and output used in the current study was found to be safe. There was a single success in converting a chronic AF to sinus rhythm.

Suicide and Life Insurance.

Much has been written about the history of suicide and, notably, about societies that condemned both the act and the actor, resulting in a perpetuation of suicide being stigmatized in many cultures. One aspect of this perceived stigmatization involves exclusionary clauses in life insurance policies that reject paying benefits to survivor-beneficiaries of the decedent if the decedent has died by suicide within a prescribed time frame. From the perspective of the individual, life insurance is designed to protect the estate of a decedent from a significant financial burden. From the insurer's perspective, there are essentially 2 reasons for having a suicide exclusion clause: limiting risk and preventing or discouraging fraud. This column examines these rationales in light of the estimated few suicides that do occur during exclusionary clause time frames. Observations are made about the effect of these clauses on those impacted by the loss of a loved one who died by suicide within the exclusionary time frame. An examination of the perspectives of both the life insurance industry and the impacted survivors of suicide decedents raises questions about what are reasonable and appropriate exclusionary clause time frames that protect both the insurer and survivor-beneficiaries. The forensic expert consulting on such cases should be cognizant of these competing perspectives and engage in therapeutic assessment whenever possible, identifying opportunities to promote thoughtful suicide postvention.

Comparison of chronic biphasic pacing versus cathodal pacing of the right ventricle on left ventricular function in sheep after myocardial infarction.

BACKGROUND: The physiological effects of biphasic pacing have not been studied in compromised hearts. METHODS: Myocardial infarction was induced in 12 sheep by high coronary artery ligation. Perioperative mortality was 33%. The surviving eight animals exhibited increased left ventricular volume and reduced percent fractional shortening. Two weeks after the infarction, sheep were implanted with atrial-triggered, right ventricular pacemaker systems capable of pacing with cathodal (cathodal pulse) and biphasic (anodal pulse followed by cathodal pulse) waveforms, and randomly assigned to an initial mode. At 3-month intervals, or whenever pacing was lost for any reason, the pacing system was switched to the alternative mode. Cardiac function was assessed at 2- to 3-week intervals through the use of echocardiograms. Successful pacing was confirmed over an average of 8 weeks in each mode. RESULTS: Cathodal pulsing had neither beneficial nor deleterious effect on the diminished cardiac performance induced by myocardial infarction. When compared to the cathodal mode, biphasic pulsing improved cardiac performance as reflected by decrease of diastolic and systolic ventricular volumes, reduction in left ventricular systolic diameter, and increases in percent fractional shortening. When compared to the unpaced state after the myocardial infarction, the percent fractional shortening was significantly increased by biphasic pacing. Concordant trends in improvement in the other cardiac parameters were also observed for the biphasic mode. No ventricular tachyarrhythmias or mortality was associated with biphasic stimulation. CONCLUSION: When compared to cathodal pacing, myocardial biphasic pacing has no safety issues in sheep that have undergone a large myocardial infarction. Importantly, biphasic pulsing elicited significant benefits in cardiac performance.

Implementation of a suicide nomenclature within two VA healthcare settings.

Suicide and suicide attempts are significant issues for military, Veterans Affairs (VA), and civilian healthcare systems. The lack of uniform terms related to self-directed violence (SDV) has inhibited epidemiological surveillance efforts, limited the generalizability of empirical studies of suicide and non-lethal forms of SDV, and complicated the implementation of evidence-based assessment and treatment strategies for individuals with suicidal thoughts and/or behaviors. The Department of Veterans Affairs recently adopted the Centers for Disease Control and Prevention's (CDC) SDV Classification System (SDVCS). This paper describes an implementation study of the SDVCS in two VA Medical Centers. The Veterans Integrated Service Network (VISN) 19 Mental Illness Research, Education and Clinical Center (MIRECC) training program for the SDVCS, including the SDVCS Clinical Tool (CT), will be discussed. Although preliminary data suggest that the CT and SDVCS are generally perceived as being acceptable and useful, further work will likely be required to facilitate widespread adoption. Potential next steps in this process are presented.

Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma.

BACKGROUND: Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4Ralpha and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum-sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. METHODS: Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. RESULTS: Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC(100) relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05-0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC(100) relative to control (P < 0.05) at nominal b.i.d. doses of 3-100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. CONCLUSION: Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma.

Can elective surgery for mandibular and zygomatic complex fractures reduce overall hospital stay without compromising outcomes? Analysis of administrative datasets by the GIRFT programme.

When patients attend the emergency department with facial fractures that require surgery and are immediately admitted, surgery can be delayed as theatre time is prioritised for other more urgent patients. One solution is to send the patient home and admit them as an elective patient at a later date. The aim of this study was to investigate the outcomes of patients admitted directly and those seen as elective patients following fracture of the mandible or zygomatic complex. Data were taken from the hospital episodes statistics (HES) dataset for 2011-2018, and all hospital admissions for mandibular and zygomatic complex fractures within the National Health Service (NHS) in England were extracted. Patients were categorised as those admitted on attendance at the emergency department and given definitive treatment during the admission, and those not admitted on attendance at the emergency department but discharged home and seen as elective admissions within 30 days of attendance. Data were available for 39 606 patients. For both types of fracture there was substantial variation between NHS trusts in the proportion of patients admitted electively and the proportion admitted directly as emergencies. Elective admission was independently associated with shorter overall stay and lower emergency readmission rates. We found no evidence that delays to definitive surgery through elective admission had a negative impact on emergency readmission rates. Patients admitted electively had a significantly shorter hospital stay.

Near Term Suicide Risk Assessment: A Commentary on the Clinical Relevance of Protective Factors.

In this article we examine the clinical relevance of protective factors to the assessment and formulation of near-term risk of death by suicide. Contrary to current clinical belief and practice, we posit that there is no evidence base to support these factors as mitigating or buffering risk for suicide for the individual patient, especially in the near-term assessment of that suicide risk. We show that evidence-based protective factors derive from population-based studies and, applicably, have relevance to public health promotion/primary prevention and are significant in informing treatment/secondary prevention, but they lack evidence to support their often-proposed role in mitigating or buffering risk for suicide on an individual basis, especially when applied to the assessment of near-term risk of suicide. Accordingly, we argue for the need for empirical study of the role protective factors may or may not play in the formulation of a patient's risk for suicide and, in the interim, for clinical caution in assuming that protective factors have any significant buffering effect on a patient's level of near-term risk.