Systemic Challenges in Internship Training for Health-Service Psychology: A Call to Action From Trainee Stakeholders.

The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

Excitonic absorption and defect-related emission in three-dimensional MoS2 pyramids.

MoS2 micro-pyramids have demonstrated interesting properties in the fields of photonics and non-linear optics. In this work, we show the excitonic absorption and cathodoluminescence (CL) emission of MoS2 micro-pyramids grown by chemical vapor deposition (CVD) on SiO2 substrates. The excitonic absorption was obtained at room and cryogenic temperatures by taking advantage of the cathodoluminescence emission of the SiO2 substrate. We detected the CL emission related to defect intra-gap states, localized at the pyramid edges and with an enhanced intensity at the pyramid basal vertices. The photoluminescence and absorption analysis provided the Stokes shift of both the A and B excitons in the MoS2 pyramids. This analysis provides new insights into the optical functionality of MoS2 pyramids. This method can be applied to other 3D structures within the 2D materials family.

Effective discrimination of gas-phase peptide conformers using TIMS-ECD-ToF MS/MS.

In the present work, four, well-studied, model peptides (e.g., substance P, bradykinin, angiotensin I and AT-Hook 3) were used to correlate structural information provided by ion mobility and ECD/CID fragmentation in a TIMS-q-EMS-ToF MS/MS platform, incorporporating an electromagnetostatic cell (EMS). The structural heterogeneity of the model peptides was observed by (i) multi-component ion mobility profiles (high ion mobility resolving power, R ∼115-145), and (ii) fast online characteristic ECD fragmentation patterns per ion mobility band (∼0.2 min). Particularly, it was demonstrated that all investigated species were probably conformers, involving cis/trans-isomerizations at X-Pro peptide bond, following the same protonation schemes, in good agreement with previous ion mobility and single point mutation experiments. The comparison between ion mobility selected ECD spectra and traditional FT-ICR ECD MS/MS spectra showed comparable ECD fragmentation efficiencies but differences in the ratio of radical (˙)/prime (') fragment species (H˙ transfer), which were associated with the differences in detection time after the electron capture event. The analysis of model peptides using online TIMS-q-EMSToF MS/MS provided complementary structural information on the intramolecular interactions that stabilize the different gas-phase conformations to those obtained by ion mobility or ECD alone.

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis.

OBJECTIVE: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA. METHOD: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-κB signaling via intra-articular delivery of an IκB kinase two antagonist to understand how local NF-κB inhibition might alter disease progression. RESULTS: Following joint injury NF-κB signaling within the knee joint was transiently increased and peaked on day 3 with an estimated 1.35 p/s/cm2/sr (95% CI 0.913.1.792 p/s/cm2/sr) fold increase in signaling when compared to control joints. Furthermore, injury resulted in the long-term development of hindpaw allodynia. Hyperalgesia withdrawal thresholds were reduced at injured knee joints, with the largest reduction occurring 2 days following injury (estimate of between group difference 129.1 g with 95% CI 60.9,197.4 g), static weight bearing on injured limbs was also reduced. Local delivery of an NF-κB inhibitor following joint injury reduced chondrocyte death and influenced the development of pain-related sensitivity but did not reduce long-term cartilage degeneration. CONCLUSION: These findings underscore the development of behavioral changes in this non-invasive loading model of PTOA and their relationships to NF-κB activation and pathology. They also highlight the potential chondroprotective effects of NF-κB inhibition shortly following joint injury despite limitations in preventing the long-term development of joint degeneration in this model of PTOA.

Matrigel-Free Laminin-Entactin Matrix to Induce Human Renal Proximal Tubule Structure Formation In Vitro.

A successful in vitro tissue model must recapitulate the native tissue features while also being reproducible. Currently, Matrigel is the principal biomaterial used to induce the formation of proximal convoluted tubules (PCTs) in vitro, because of its similar composition and structure with the kidney tubular basement membrane and the presence of critical growth factors. However, Matrigel is not well-defined, and batch-to-batch variability is a significant issue. Here, we define a Matrigel-free method, using a laminin-entactin (L-E) matrix to support the formation of proximal tubular-like structures in vitro using immortalized human renal epithelial cells (RPTEC/TERT1) cocultured with murine fibroblast stromal cells (FOXD1lacZ+). The matrix supports the presence of specific components of the tubular basement membrane (laminin, entactin/nidogen, and heparan sulfate proteoglycan) in addition to fibroblast growth factor 8a (FGF-8a). The matrix also induces tubulogenesis, leading to the formation of PCTs based on several key markers, including E-cadherin, aquaporin-1, and Na+/K+ ATPase. Moreover, these PCT structures displayed cell polarity and a well-defined lumen after 18 days in culture. This laminin-entactin (L-E) matrix constitutes a defined and consistent biomaterial that can be used in kidney tissue engineering for understanding in vitro proximal tubule development and for nephrotoxicity studies.

Demonstration of Muon-Beam Transverse Phase-Space Compression.

We demonstrate efficient transverse compression of a 12.5 MeV/c muon beam stopped in a helium gas target featuring a vertical density gradient and crossed electric and magnetic fields. The muon stop distribution extending vertically over 14 mm was reduced to a 0.25 mm size (rms) within 3.5 µs. The simulation including cross sections for low-energy µ^{+}-He elastic and charge exchange (µ^{+}↔ muonium) collisions describes the measurements well. By combining the transverse compression stage with a previously demonstrated longitudinal compression stage, we can improve the phase space density of a µ^{+} beam by a factor of 10^{10} with 10^{-3} efficiency.

Estimating neuronal conductance model parameters using dynamic action potential clamp.

BACKGROUND: Parameterization of neuronal membrane conductance models relies on data acquired from current clamp (CC) or voltage clamp (VC) recordings. Although the CC approach provides key information on a neuron's firing properties, it is often difficult to disentangle the influence of multiple conductances that contribute to the excitation properties of a real neuron. Isolation of a single conductance using pharmacological agents or heterologous expression simplifies analysis but requires extensive VC evaluation to explore the complete state behavior of the channel of interest. NEW METHOD: We present an improved parameterization approach that uses data derived from dynamic action potential clamp (DAPC) recordings to extract conductance equation parameters. We demonstrate the utility of the approach by applying it to the standard Hodgkin-Huxley conductance model although other conductance models could be easily incorporated as well. RESULTS: Using a fully simulated setup we show that, with as few as five action potentials previously recorded in DAPC mode, sodium conductance equation parameters can be determined with average parameter errors of less than 4% while action potential firing accuracy approaches 100%. In real DAPC experiments, we show that by "training" our model with five or fewer action potentials, subsequent firing lasting for several seconds could be predicted with ˜96% mean firing rate accuracy and 94% temporal overlap accuracy. COMPARISON WITH EXISTING METHODS: Our DAPC-based approach surpasses the accuracy of VC-based approaches for extracting conductance equation parameters with a significantly reduced temporal overhead. CONCLUSION: DAPC-based approach will facilitate the rapid and systematic characterization of neuronal channelopathies.

N-(p-amylcinnamoyl) anthranilic acid attenuates remedial effects of memantine on memory deficits following intracerebroventricular streptozotocin administration in rats.

N-(p-amylcinnamoyl) anthranilic acid (ACA) is a blocker of transient receptor potential melastatin-2 (TRPM2) which is a non-selective, Ca2+-permeable and oxidative stress sensor cation channel. Intracerebroventricular (ICV) streptozotocin (STZ) induction successfully generates spatial memory deficits in rats. The purpose of this study was to investigate effects of ACA on a rat model of STZ-induced learning and memory deficits. A total of 60 Wistar rats randomly divided into six groups; (1) control, (2) sham-operated, (3) ICV-STZ administered, (4) ICV-STZ + memantine (5 mg/kg i.p.), (5) ICV-STZ + ACA (25 mg/kg i.p.) and (6) a combination therapy group, ICV-STZ + ACA (25 mg/kg) + memantine (5 mg/kg). Effects of the drugs on spatial memory deficits were appraised in Morris water maze (MWM) apparatus. Anxiety-like behavior of the rats were also assessed by using both the elevated plus maze (EPM) and open field maze (OFM) apparatuses. Western blot analysis of hippocampal tissues revealed TRPM2-L channel protein expression levels. Serum levels of tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Memantine treatment ameliorated the spatial memory deficits induced, as evidenced by the MWM tests. However, ACA treatment did not provide any improvement, instead positive effects of memantine were attenuated by ACA treatment. Western blot analysis in hippocampal tissues showed that TRPM2-L protein expression was markedly suppressed in ICV-STZ administered group. The ACA treatment reversed that suppression. Surprisingly, the memantine treatment resulted in overexpression of TRPM2-L, to a certain extent. Examination of the rats in EPM and OFM apparatuses, as a display of anxiety-like behavior, did not reveal any marked difference among groups. Serum levels of TNF-α and MDA also did not vary significantly among groups, as well. Conclusively, our findings showed for the first time that TRPM2-L protein expression was significantly suppressed in the ICV-STZ induced memory deficit model. Even though ACA reversed this suppression, no improvement in spatial memory was observed following ACA treatment.

Active spectroscopy measurements of the deuterium temperature, rotation, and density from the core to scrape off layer on the DIII-D tokamak (invited).

Main-ion charge exchange recombination spectroscopy (MICER) uses the neutral beam induced D α spectrum to measure the local deuterium ion (D+) temperature, rotation, and density, as well as parameters related to the neutral beams, fast ions, and magnetic field. An edge MICER system consisting of 16 densely packed chords was recently installed on DIII-D, extending the MICER technique from the core to the pedestal and steep gradient region of H-mode plasmas where the D+ and commonly measured impurity ion properties can differ significantly. A combination of iterative collisional radiative modeling techniques and greatly accelerated spectral fitting allowed the extension of this diagnostic technique to the plasma edge where the steep gradients introduce significant diagnostic challenges. The importance of including the fast ion D α emission in the fit to the spectrum for the edge system is investigated showing that it is typically not important except for cases which can have significant fast ion fractions near the plasma edge such as QH-mode. Example profiles from an Ohmic L-mode and a high power ITER baseline case show large differences in the toroidal rotation of the two species near the separatrix including a strong co-current D+ edge rotation. The measurements and analysis demonstrate the state of the art in active spectroscopy and integrated modeling for diagnosing fusion plasmas and the importance of direct main ion measurements.

Diagnosis and treatment of necrotising otitis externa and diabetic foot osteomyelitis - similarities and differences.

OBJECTIVE: Necrotising otitis externa is a severe inflammatory process affecting soft tissue and bone, mostly in diabetic patients. Diabetic patients are also at risk of diabetic foot osteomyelitis, another inflammatory condition involving soft tissue and bone. This review aimed to describe the similarities and differences of these entities in an attempt to further advance the management of necrotising otitis externa. METHOD: A PubMed search was conducted using the key words 'otitis externa', 'necrotising otitis externa', 'malignant otitis externa', 'osteomyelitis' and 'diabetic foot'.Results and conclusionThe similarities regarding patient population and pathophysiology between necrotising otitis externa and diabetic foot osteomyelitis raise basic questions concerning the effects of long-standing diabetes on the external ear. The concordance between local swabs and bone cultures in diabetic foot osteomyelitis is less than 50 per cent. If this holds true also to necrotising otitis externa, the role of deep tissue cultures should be strongly considered. Similar to diabetic foot osteomyelitis, magnetic resonance imaging should be considered in selected necrotising otitis externa subgroups.

Silk fibroin preserves beta cell function under inflammatory stress while stimulating islet cell surface GLUT2 expression.

Silk fibroin is a novel biomaterial for enhancing transplanted islet cell function and survival. This study investigated whether silk fibroin may have unique properties that improve islet function in the face of inflammatory-mediated stress during transplantation. Murine islet function was tested in vitro with either silk fibroin or alginate and challenged with inflammatory cytokines. The glucose-stimulated insulin secretion index for all conditions decreased with inflammatory cytokines, but was better preserved for islets exposed to silk compared to those exposed to alginate or medium. GLUT2 transporter expression on the cell surface of islets exposed to silk was increased compared to alginate or medium alone. Upon cytokine stress, a greater percentage of islet cells exposed to silk expressed GLUT2 on their surface. We conclude that preconditioning islets with silk fibroin stimulates islet cell surface GLUT2 expression, an increase, which persists under inflammatory stress, and may improve islet engraftment and function after transplantation.

In vitro 3D regeneration-like growth of human patient brain tissue.

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 µm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models.

Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions.

Type III solar radio bursts are the Sun's most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5-10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.

Residence time effects on technetium reduction in slag-based cementitious materials.

A long-term disposal of technetium-99 (99Tc) has been considered in a type of cementitious formulation, slag-based grout, at the U.S. Department of Energy, Savannah River Site, Aiken SC, U.S.A. Blast furnace slag, which contains S and Fe electron donors, has been used in a mixture with fly ash, and Portland cement to immobilize 99Tc(VII)O4-(aq) in low level radioactive waste via reductive precipitation reaction. However the long-term stability of Tc(IV) species is not clearly understood as oxygen gradually diffuses into the solid structure. In this study, aging effects of Tc speciation were investigated as a function of depth (<2.5cm) in slag-based grout using X-ray absorption spectroscopy. All of Fe(II) in solids was oxidized to Fe(III) after 117d. However, elemental S, sulfide, and sulfoxide persists at the 0-8mm depths even after 485d, suggesting the presence of a reduced zone below the surface few millimeters. Pertechnetate was successfully reduced to Tc(IV) after 29d. Distorted hydrolyzed Tc(IV) octahedral molecules were partially sulfidized and or polymerized at all depths (0-8mm) and were stable in 485d aged sample. The results of this study suggest that variable S species contribute to stabilize the partially sulfidized Tc(IV) species in aged slag-based grout.

Rare clinically significant hepatic events and hepatitis B reactivation occur more frequently following rather than during direct-acting antiviral therapy for chronic hepatitis C: Data from a national US cohort.

Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; ≥300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations ≥300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy.

A mildly relativistic wide-angle outflow in the neutron-star merger event GW170817.

GW170817 was the first gravitational-wave detection of a binary neutron-star merger. It was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 40 megaparsecs. It has been proposed that the observed γ-ray, X-ray and radio emission is due to an ultra-relativistic jet being launched during the merger (and successfully breaking out of the surrounding material), directed away from our line of sight (off-axis). The presence of such a jet is predicted from models that posit neutron-star mergers as the drivers of short hard-γ-ray bursts. Here we report that the radio light curve of GW170817 has no direct signature of the afterglow of an off-axis jet. Although we cannot completely rule out the existence of a jet directed away from the line of sight, the observed γ-ray emission could not have originated from such a jet. Instead, the radio data require the existence of a mildly relativistic wide-angle outflow moving towards us. This outflow could be the high-velocity tail of the neutron-rich material that was ejected dynamically during the merger, or a cocoon of material that breaks out when a jet launched during the merger transfers its energy to the dynamical ejecta. Because the cocoon model explains the radio light curve of GW170817, as well as the γ-ray and X-ray emission (and possibly also the ultraviolet and optical emission), it is the model that is most consistent with the observational data. Cocoons may be a ubiquitous phenomenon produced in neutron-star mergers, giving rise to a hitherto unidentified population of radio, ultraviolet, X-ray and γ-ray transients in the local Universe.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.

The role of explorative tympanotomy in patients with sudden sensorineural hearing loss with and without perilymphatic fistula.

PURPOSE: The purpose of this study was to describe the role of explorative tympanotomy in patients with Profound Sudden Sensorineural Hearing Loss (SSNHL) without clinical evidence of perilymphatic or labyrinthine fistula and to compare intraoperative findings with the postoperative hearing outcome. STUDY DESIGN: Retrospective study of all patients diagnosed with SSNHL who underwent explorative tympanotomy between 2002 and 2005. SETTINGS: Tertiary care university-affiliated hospital. SUBJECTS AND METHODS: Eighty-two patients were diagnosed with unilateral profound SSNHL and underwent tympanotomy with sealing of the round and oval windows. Values of pure tone audiograms and percentage hearing loss of patients with and without intraoperative diagnosed perilymphatic fistula (PLF) were compared and analyzed. RESULTS: PLF was diagnosed in 28% cases intraoperatively. In most cases, hearing improved significantly after surgery. Interestingly, patients with PLF had a 2.4 times greater decrease of percentage hearing loss compared to patients without PLF. CONCLUSIONS: Explorative tympanotomy seems to be useful in patients with profound SSNHL. Patients with PLF benefit more from the surgical procedure and have better outcome than patients without PLF.