Divergence beneath the Brillouin sphere and the phenomenology of prediction error in spherical harmonic series approximations of the gravitational field.

The Brillouin sphere is defined as the smallest sphere, centered at the origin of the geocentric coordinate system, that incorporates all the condensed matter composing the planet. The Brillouin sphere touches the Earth at a single point, and the radial line that begins at the origin and passes through that point is called the singular radial line. For about 60 years there has been a persistent anxiety about whether or not a spherical harmonic (SH) expansion of the external gravitational potential,V, will converge beneath the Brillouin sphere. Recently, it was proven that the probability of such convergence is zero. One of these proofs provided an asymptotic relation, called Costin's formula, for the upper bound,EN, on the absolute value of the prediction error,eN, of a SH series model,VN(θ,λ,r), truncated at some maximum degree,N=nmax. When the SH series is restricted to (or projected onto) a particular radial line, it reduces to a Taylor series (TS) in1/r. Costin's formula isEN≃BN-b(R/r)N, whereRis the radius of the Brillouin sphere. This formula depends on two positive parameters:b, which controls the decay of error amplitude as a function ofNwhenris fixed, and a scale factorB. We show here that Costin's formula derives from a similar asymptotic relation for the upper bound,Anon the absolute value of the TS coefficients,an, for the same radial line. This formula,An≃Kn-k, depends on degree,n, and two positive parameters,kandK, that are analogous tobandB. We use synthetic planets, for which we can compute the potential,V, and also the radial component of gravitational acceleration,gr=∂V/∂r, to hundreds of significant digits, to validate both of these asymptotic formulas. Let superscriptVrefer to asymptotic parameters associated with the coefficients and prediction errors for gravitational potential, and superscriptgto the coefficients and predictions errors associated withgr. For polyhedral planets of uniform density we show thatbV=kV=7/2andbg=kg=5/2almost everywhere. We show that the frequency of oscillation (around zero) of the TS coefficients and the series prediction errors, for a given radial line, is controlled by the geocentric angle,α, between that radial line and the singular radial line. We also derive useful identities connectingKV,BV,Kg, andBg. These identities are expressed in terms of quotients of the various scale factors. The only other quantities involved in these identities areαandR. The phenomenology of 'series divergence' and prediction error (whenr < R) can be described as a function of the truncation degree,N, or the depth,d, beneath the Brillouin sphere. For a fixedr⩽R, asNincreases from very low values, the upper error boundENshrinks until it reaches its minimum (best) value whenNreaches some particular or optimum value,Nopt. WhenN>Nopt, prediction error grows asNcontinues to increase. Eventually, whenN≫Nopt, prediction errors increase exponentially with risingN. If we fix the value ofNand allowR/rto vary, then we find that prediction error in free space beneath the Brillouin sphere increases exponentially with depth,d, beneath the Brillouin sphere. Becausebg=bV-1everywhere, divergence driven prediction error intensifies more rapidly forgrthan forV, both in terms of its dependence onNandd. If we fix bothNandd, and focus on the 'lateral' variations in prediction error, we observe that divergence and prediction error tend to increase (as doesB) as we approach high-amplitude topography.

Safety Evaluation in Iterative Development of Wearable Patches for Aripiprazole Tablets With Sensor: Pooled Analysis of Clinical Trials.

BACKGROUND: Wearable sensors in digital health may pose a risk for skin irritation through the use of wearable patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite; Otsuka America Pharmaceutical, Inc) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder. AS includes aripiprazole tablets with an embedded ingestible event marker, a wearable sensor attached to the skin through a wearable patch, a smartphone app, and a web-based portal. To continuously improve the final product, successive iterations of wearable patches were developed, including raisin patch version 4 (RP4), followed by disposable wearable sensor version 5 (DW5), and then reusable wearable sensor version 2 (RW2). OBJECTIVE: This analysis pooled safety data from clinical studies in adult participants using the RP4, DW5, and RW2 wearable patches of AS and evaluated adverse events related to the use of wearable patches. METHODS: Safety data from 12 studies in adults aged 18-65 years from May 2010 to August 2020 were analyzed. All studies evaluated safety, with studies less than 2 weeks also specifically examining human factors associated with the use of the components of AS. Healthy volunteers or patients with schizophrenia, bipolar I disorder, or major depressive disorder were enrolled; those who were exposed to at least 1 wearable patch were included in the safety analysis. Adverse events related to the use of a wearable patch were evaluated. Abrasions, blisters, dermatitis, discoloration, erythema, irritation, pain, pruritus, rash, and skin reactions were grouped as skin irritation events (SIEs). All statistical analyses were descriptive. RESULTS: The analysis included 763 participants (mean [SD] age 42.6 [12.9] years; White: n=359, 47.1%; and male: n=420, 55%). Participants were healthy volunteers (n=269, 35.3%) or patients with schizophrenia (n=402, 52.7%), bipolar I disorder (n=57, 7.5%), or major depressive disorder (n=35, 4.6%). Overall, 13.6% (104/763) of the participants reported at least 1 SIE, all of which were localized to the wearable patch site. Incidence of ≥1 patch-related SIEs was seen in 18.1% (28/155), 14.2% (55/387), and 9.2% (28/306) of participants who used RP4, DW5, and RW2, respectively. Incidence of SIE-related treatment discontinuation was low, which is reported by 1.9% (3/155), 3.1% (12/387), and 1.3% (4/306) of participants who used RP4, DW5, and RW2, respectively. CONCLUSIONS: The incidence rates of SIEs reported as the wearable patch versions evolved from RP4 through RW2 suggest that information derived from reported adverse events may have informed product design and development, which could have improved both tolerability and wearability of successive products. TRIAL REGISTRATION: Clinicaltrials.gov NCT02091882, https://clinicaltrials.gov/study/NCT02091882; Clinicaltrials.gov NCT02404532, https://clinicaltrials.gov/study/NCT02404532; Clinicaltrials.gov NCT02722967, https://clinicaltrials.gov/study/NCT02722967; Clinicaltrials.gov NCT02219009, https://clinicaltrials.gov/study/NCT02219009; Clinicaltrials.gov NCT03568500, https://clinicaltrials.gov/study/NCT03568500; Clinicaltrials.gov NCT03892889, https://clinicaltrials.gov/study/NCT03892889.

Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

History of childhood physical abuse is associated with gut microbiota diversity among adult psychiatric inpatients.

BACKGROUND: Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients. METHODS: 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community. RESULTS: Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon item-level analysis, history of childhood physical abuse was uniquely associated with beta diversity. Linear Discriminant Analysis Effect Size (LefSe) analyses revealed that childhood physical abuse was associated with abundance of distinct bacterial taxa associated with inflammation. LIMITATIONS: This study did not account for dietary differences, though diet was highly restricted as all participants were psychiatric inpatients. Absolute variance accounted for by the taxa was small though practically meaningful. The study was not powered for full subgroup analysis based on race and ethnicity. CONCLUSIONS: This study is among the first to demonstrate a relationship between childhood physical abuse and gut microbiota composition among adult psychiatric patients. These findings suggest that early childhood adverse events may have long-conferred systemic consequences. Future efforts may target the gut microbiota for the prevention and/or treatment of psychiatric and medical risk associated with traumatic life events.

Differential co-expression networks of the gut microbiota are associated with depression and anxiety treatment resistance among psychiatric inpatients.

BACKGROUND: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients. METHODS: In a sample of convenience, 100 psychiatric inpatients provided clinical data at admission and discharge; fecal samples were collected early during the hospitalization. Whole genome shotgun sequencing methods were used to process samples. DiffCoEx was used to identify clusters of microbial features significantly different based on treatment resistance status. Once overlapping features were identified, a knowledge-mining tool was used to review the literature using a list of microbial species/pathways and a select number of medical subject headlines (MeSH) terms relevant for depression, anxiety, and brain-gut-axis dysregulation. Network analysis used overlapping features to identify microbial interactions that could impact treatment resistance. RESULTS: DiffCoEx analyzed 10,403 bacterial features: 43/44 microbial features associated with depression treatment resistance overlapped with 43/114 microbial features associated with anxiety treatment resistance. Network analysis resulted in 8 biological interactions between 16 bacterial species. Clostridium perfringens evidenced the highest connection strength (0.95). Erysipelotrichaceae bacterium 6_1_45 has been most widely examined, is associated with inflammation and dysbiosis, but has not been associated with depression or anxiety. CONCLUSION: DiffCoEx potentially identified gut bacteria biomarker candidates of depression and anxiety treatment-resistance. Future efforts in psychiatric microbiology should examine the mechanistic relationship of identified pro-inflammatory species, potentially contributing to a biomarker-based algorithm for treatment resistance.

Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.

BACKGROUND: Suboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate. OBJECTIVE: The primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence. METHODS: This open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS. RESULTS: We enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers. CONCLUSIONS: There was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449.

Healthcare Provider Engagement with a Novel Dashboard for Tracking Medication Ingestion: Impact on Treatment Decisions and Clinical Assessments for Adults with Schizophrenia.

Purpose: Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods: Participants used AS for 3-6 months. HCPs were instructed to check the dashboard regularly, identify features used, and report impact on treatment decisions. After stratifying HCPs by frequency of dashboard checks and resulting treatment decisions, changes from baseline were calculated for Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI)-Severity of Illness and CGI-Improvement (CGI-I), and Personal and Social Performance (PSP), and compared using Mann-Whitney U-tests and rank-biserial correlation coefficient (r) effect sizes. Results: To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: -9.2 versus -3.1 [p=0.0002]), PANSS positive subscale (-3.2 versus -1.5 [p=0.003]), PANSS general subscale (-4.3 versus -1.2 [p=0.02]), and Marder factor for negative symptoms (-1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion: This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.

Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia.

Purpose: A recent, phase 3b, mirror-image clinical trial of outpatients with schizophrenia found that use of aripiprazole tablets with sensor (AS; Abilify MyCite®, comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptom-severity measures assessed by clinical raters. Participants and Methods: This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18-65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated. Results: A total of 277 outpatients were enrolled (discontinued, n = 164; moderate engagement, n = 63; high engagement, n = 50). All groups experienced symptom improvement from baseline to end-of-study, with significant changes in the more-engaged groups. Highly engaged participants showed significant improvement for all clinical scores and subscores (all P < 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement. Conclusion: Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.

Functional Rehabilitation: An Integrated Treatment Model for Patients With Complex Physical and Psychiatric Conditions.

The health care delivery system in the United States, structured to provide single-disease care, presents unique challenges for patients with complex physical and psychiatric comorbidities. Patients in these populations are often referred to multiple specialty clinics, encounter little continuity of care or collaboration among their providers, incur high health care costs, and experience poor treatment outcomes. Given these barriers, questions remain about the extent to which siloed and fragmented care, as opposed to the complex nature of the illnesses themselves, contribute to poor outcomes. If given the opportunity to receive well-integrated, consistent, and personalized care, can patients with historically difficult-to-treat comorbid medical and mental illnesses make progress? This article describes an innovative model of care called functional rehabilitation that is designed to address existing barriers in treatment. The functional rehabilitation program seeks to disrupt the escalating effects of interacting comorbidities by offering highly collaborative treatment from a small team of clinicians, personalized interventions using a shared decision-making framework, multipronged treatment options, colocation in a large hospital system, and significant 1:1 time with patients. The article includes a case example with longitudinal outcome data that illustrates how progress can be made with appropriate programmatic supports. Future research should examine the cost-effectiveness of this model of care.

Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Phase 3b Multicenter, Prospective, Open-label Trial to Evaluate the Effects of a Digital Medicine System on Inpatient Psychiatric Hospitalization Rates for Adults With Schizophrenia.

Objective: Inpatient psychiatric admissions drive the financial burden of schizophrenia, and medication adherence remains challenging. We assessed whether aripiprazole tablets with sensor (AS; system includes ingestible event-marker sensor, wearable sensor patches, and smartphone application) could reduce psychiatric hospitalizations compared with oral standard-of-care (SOC) antipsychotics.Methods: This phase 3b, mirror-image clinical trial was conducted from April 29, 2019-August 11, 2020, in adults with schizophrenia with ≥ 1 hospitalization in the previous 48 months who had been prescribed oral SOC for the preceding 6 months (retrospective phase). All participants used AS for at least 3 months and up to 6 months. Primary endpoint was the inpatient psychiatric hospitalization rate in the modified intent-to-treat (mITT; n = 113) population during prospective months 1-3 versus retrospective phase. Proportion of days covered by medication was the secondary endpoint. Safety endpoints included adverse events related to the medication or patch and suicidality.Results: AS significantly reduced hospitalizations during prospective months 1-3 (-9.7%) and months 1-6 (-21.3% [P ≤ .001 for all comparisons]) in the mITT population versus the corresponding retrospective phase. AS use improved confirmed medication ingestion by 26.5 percentage points in prospective months 1-3 (P ≤ .001) and reduced PANSS scores. Patches were well-tolerated, and no participant reported changes in suicide risk.Conclusions: Compared with oral SOC, AS reduced inpatient psychiatric hospitalization rates for adults with mild-to-moderate schizophrenia. The AS system may aid medication ingestion and is associated with improvements in symptoms, potentially reducing acute-care needs among patients with schizophrenia.Trial Registration: ClinicalTrials.gov identifier: NCT03892889.

Personality trait domains predict psychiatric symptom and functional outcomes.

A review of high intensity, high dose mentalization-based inpatient psychiatric treatment indicated large effect-size reductions in symptoms of depression, anxiety, somatization, and improving emotion-regulation functioning (Allen et al., 2017). This study examined the impact of pathological personality traits has on baseline symptoms and functioning, as well as their impact on the longitudinal course in a large cohort of adult inpatient psychiatric sample (N = 804). The Personality Inventory for DSM-5 (PID-5; Krueger et al., 2012) was used to assess trait domains impact on longitudinal outcomes (anxiety, depression, somatic symptoms, and functional impairment) using hierarchical repeated measures modeling. Results indicate Negative Affectivity and Detachment were related to higher admission severity in all four outcome domains. Psychoticism was related to somatic symptoms, while Antagonism and Disinhibition were related to functional impairment. Paradoxically, when symptoms were plotted over 2-week intervals during hospitalization, patients with higher admission PID-5 trait scores exhibited greater improvement over time. The PID-5 appears to contribute to prediction of treatment outcome response above and beyond demographic and burden of illness. Importantly, the findings add to a growing body of literature indicating that impairments in personality traits do not preclude positive treatment response, particularly when treatments target pathological personality features. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Energy Calibration of Nonlinear Microcalorimeters with Uncertainty Estimates from Gaussian Process Regression.

The nonlinear energy response of cryogenic microcalorimeters is usually corrected through an empirical calibration. X-ray or gamma-ray emission lines of known shape and energy anchor a smooth function that generalizes the calibration data and converts detector measurements to energies. We argue that this function should be an approximating spline. The theory of Gaussian process regression makes a case for this functional form. It also provides an important benefit previously absent from our calibration method: a quantitative uncertainty estimate for the calibrated energies, with lower uncertainty near the best-constrained calibration points.

Predicting depression outcomes throughout inpatient treatment using the general and specific personality disorder factors.

BACKGROUND: Clinical intuition suggests that personality disorders hinder the treatment of depression, but research findings are mixed. One reason for this might be the way in which current assessment measures conflate general aspects of personality disorders, such as overall severity, with specific aspects, such as stylistic tendencies. The goal of this study was to clarify the unique contributions of the general and specific aspects of personality disorders to depression outcomes. METHODS: Patients admitted to the Menninger Clinic, Houston, between 2012 and 2015 (N = 2352) were followed over a 6-8-week course of multimodal inpatient treatment. Personality disorder symptoms were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition Axis II Personality Screening Questionnaire at admission, and depression severity was assessed using the Patient Health Questionnaire-9 every fortnight. General and specific personality disorder factors estimated with a confirmatory bifactor model were used to predict latent growth curves of depression scores in a structural equation model. RESULTS: The general factor predicted higher initial depression scores but not different rates of change. By contrast, the specific borderline factor predicted slower rates of decline in depression scores, while the specific antisocial factor predicted a U shaped pattern of change. CONCLUSIONS: Personality disorder symptoms are best represented by a general factor that reflects overall personality disorder severity, and specific factors that reflect unique personality styles. The general factor predicts overall depression severity while specific factors predict poorer prognosis which may be masked in prior studies that do not separate the two.

Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

A Naturalistic Study of Time to Recovery in Adults with Treatment-refractory Disorders.

Objectives: Individuals with treatment-refractory disorders have high comorbidity. There is little information on whether recovery is possible and how long it might require. We focused on the individual's recovery using a broad measure of psychopathology, regardless of the variety of disorders present.Methods: We recruited 226 adults [mean age 31.0, SD = 10.3; 75.2% female] entering residential treatment for treatment-refractory disorders to delineate their course and outcome. Individuals received periodic Longitudinal Interval Follow-along Evaluation interviews for symptoms and functioning variables for up to 14 years. Periodic psychodynamic and relationship vignette interviews were rated with the Psychodynamic Conflict Rating Scales (PCRS) for a subgroup of 54 subjects. Outcome variables included modeled rates of change, final scores, time to recovery, and time to attaining healthy adaptive functioning, using Kaplan-Meier estimates from time-to-event analyses.Results: Recovery of PCRS Pathological Functioning occurred in 12 (22%) of 54 subjects rated: median time-to-recovery = 11.63 years (CI: 9.64- upper number not calculable). Eight (14.81%) subjects also developed healthy adaptive functioning, with the time-to-attainment for the first quartile at 10.95 years (CI: 7.87 - upper bound not calculable). Recovery from psychopathology was significantly associated with a median percentage recovered in the domains of symptoms (64.29%), functioning (87.50%), and psychodynamic functioning (50%). Although attaining healthy adaptive functioning was less common, it was highly associated with already achieving recovery from dynamic psychopathology, [OR = 57.40, CI 5.80 - 567.83, p = .0001].Conclusions: These results provided convergent validation of recovery in psychodynamic psychopathology. Some recovered individuals also attained healthy adaptive functioning, which took somewhat longer.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

Absolute energies and emission line shapes of the L x-ray transitions of lanthanide metals.

We use an array of transition-edge sensors, cryogenic microcalorimeters with 4 eV energy resolution, to measure L x-ray emission-line profiles of four elements of the lanthanide series: praseodymium, neodymium, terbium, and holmium. The spectrometer also surveys numerous x-ray standards in order to establish an absolute-energy calibration traceable to the international system of units for the energy range 4 keV to 10 keV. The new results include emission line profiles for 97 lines, each expressed as a sum of one or more Voigt functions; improved absolute energy uncertainty on 71 of these lines relative to existing reference data; a median uncertainty on the peak energy of 0.24 eV, four to ten times better than the median of prior work; and six lines that lack any measured values in existing reference tables. The 97 lines comprise nearly all of the most intense L lines from these elements under broad-band x-ray excitation. The work improves on previous measurements made with a similar cryogenic spectrometer by the use of sensors with better linearity in the absorbed energy and a gold x-ray absorbing layer that has a Gaussian energy-response function. It also employs a novel sample holder that enables rapid switching between science targets and calibration targets with excellent gain balancing. Most of the results for peak energy values shown here should be considered as replacements for the currently tabulated standard reference values, while the line shapes given here represent a significant expansion of the scope of available reference data.

Attachment Style Mediates the Relationship between Trauma and Somatic Distress among Individuals with Serious Mental Illness.

Objective: Individuals with mental illnesses severe enough to require psychiatric hospitalization often have significant trauma histories, have developed maladaptive attachment styles, and experience comorbid somatic distress. Gaining an understanding about the interaction of such factors may lead to prioritizing interventions that target factors that mediate the relationship between trauma and adverse somatic distress. Prior research has examined various mediation models, but results have been mixed and conducted only on outpatient samples.Method: Participants (47.7% female) in a large sample (N = 2702) with a mean age of 34.62 (SD = 14.7) were enrolled in a specialist inpatient program and completed self-report measures pertaining to demographics, attachment insecurity, lifetime trauma exposure, and somatic distress within 72 hours of admission. The dimensions of attachment insecurity (i.e., attachment anxiety and attachment avoidance) were tested as parallel mediators in the relationship between lifetime trauma exposure and somatic distress.Results: The mediation analyses revealed that attachment anxiety and avoidance partially mediated the relationship between lifetime trauma exposure and somatic distress.Conclusions: These results are the first to date to implicate both attachment anxiety and avoidance as mediators between trauma exposure and somatic distress in a high acuity sample. Although the results do not imply causality, they do call attention to social-cognitive factors related to somatic distress and highlight the importance of considering attachment styles as a possible contributor to comorbid physical symptoms in patients with trauma exposure.