Spiritual and Religious Considerations of Michigan Counseling Association Members

This study investigated Michigan Counseling Association members’ perceptions of spirituality and religion in the therapeutic process. Specifically, this study sought to find out if spirituality and religion were important in the lives of counselors; how they defi ne these concepts; if they have received training in working with these issues in counseling; and if they perceive clients as coming to counseling with spiritual or religious issues. This study confi rmed that overall, Michigan counselors consider themselves religious and/or spiritual. Counselors generally did not perceive their clients as coming to counseling with spiritual or religious issues. The majority of counselors reported they did not receive training in these areas

Oxy-functionalization of nucleophilic rhenium(I) metal carbon bonds catalyzed by selenium(IV)

We report that SeO_2 catalyzes the facile oxy-functionalization of (CO)_5Re(I)-Me^(δ−) with IO_4− to generate methanol. Mechanistic studies and DFT calculations reveal that catalysis involves methyl group transfer from Re to the electrophilic Se center followed by oxidation and subsequent reductive functionalization of the resulting CH_3Se(VI) species. Furthermore, (CO)_3Re(I)(Bpy)-R (R = ethyl, n-propyl, and aryl) complexes show analogous transfer to SeO_2 to generate the primary alcohols. This represents a new strategy for the oxy-functionalization of M−R^(δ−) polarized bonds

Fluctuation-Response Relations for Multi-Time Correlations

We show that time-correlation functions of arbitrary order for any random variable in a statistical dynamical system can be calculated as higher-order response functions of the mean history of the variable. The response is to a ``control term'' added as a modification to the master equation for statistical distributions. The proof of the relations is based upon a variational characterization of the generating functional of the time-correlations. The same fluctuation-response relations are preserved within moment-closures for the statistical dynamical system, when these are constructed via the variational Rayleigh-Ritz procedure. For the 2-time correlations of the moment-variables themselves, the fluctuation-response relation is equivalent to an ``Onsager regression hypothesis'' for the small fluctuations. For correlations of higher-order, there is a new effect in addition to such linear propagation of fluctuations present instantaneously: the dynamical generation of correlations by nonlinear interaction of fluctuations. In general, we discuss some physical and mathematical aspects of the {\it Ans\"{a}tze} required for an accurate calculation of the time correlations. We also comment briefly upon the computational use of these relations, which is well-suited for automatic differentiation tools. An example will be given of a simple closure for turbulent energy decay, which illustrates the numerical application of the relations.Comment: 28 pages, 1 figure, submitted to Phys. Rev.

Dewetting of thin films on heterogeneous substrates: Pinning vs. coarsening

We study a model for a thin liquid film dewetting from a periodic heterogeneous substrate (template). The amplitude and periodicity of a striped template heterogeneity necessary to obtain a stable periodic stripe pattern, i.e. pinning, are computed. This requires a stabilization of the longitudinal and transversal modes driving the typical coarsening dynamics during dewetting of a thin film on a homogeneous substrate. If the heterogeneity has a larger spatial period than the critical dewetting mode, weak heterogeneities are sufficient for pinning. A large region of coexistence between coarsening dynamics and pinning is found.Comment: 4 pages, 4 figure

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

Silent progression in disease activity-free relapsing multiple sclerosis.

ObjectiveRates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.MethodsDisability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates.ResultsRelapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05).InterpretationLong-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666

Is Mislocalization during saccades related to the position of the saccade target within the image or to the gaze position at the end of the saccade?

A stimulus that is flashed around the time of a saccade tends to be mislocalized in the direction of the saccade target. Our question is whether the mislocalization is related to the position of the saccade target within the image or to the gaze position at the end of the saccade. We separated the two with a visual illusion that influences the perceived distance to the target of the saccade and thus saccade endpoint without affecting the perceived position of the saccade target within the image. We asked participants to make horizontal saccades from the left to the right end of the shaft of a Müller-Lyer figure. Around the time of the saccade, we flashed a bar at one of five possible positions and asked participants to indicate its location by touching the screen. As expected, participants made shorter saccades along the fins-in (<->) configuration than along the fins-out (>-<) configuration of the figure. The illusion also influenced the mislocalization pattern during saccades, with flashes presented with the fins-out configuration being perceived beyond flashes presented with the fins-in configuration. The difference between the patterns of mislocalization for bars flashed during the saccade for the two configurations corresponded quantitatively with a prediction based on compression towards the saccade endpoint considering the magnitude of the effect of the illusion on saccade amplitude. We conclude that mislocalization is related to the eye position at the end of the saccade, rather than to the position of the saccade target within the image

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

OBJECTIVE: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. METHODS: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. RESULTS: sNfL levels were increased both in 10 AL/PNP+ patients (p  I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. CONCLUSION: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis