Attenuated psychosis symptoms are related to working alliance between therapist and service user.

AIM: Many trials have demonstrated the efficacy of specific therapy modalities for individuals with attenuated psychosis symptoms (APS). Less is known regarding mechanisms behind positive outcomes, including the role of nonspecific therapeutic factors. This study explored working alliance (WA) in a clinic serving individuals with APS to see how WA changed across the course of treatment and its relation to APS. METHODS: Session level APS and WA data was available for 12 individuals of diverse racial and gender identity, (M = 48 sessions each). Multilevel models with random intercepts tested change in WA and APS over time, and cross-sectional and prospective relations. RESULTS: WA increased and APS decreased over time. Cross sectionally, WA and APS were inversely related. Prospective relations were non-significant. CONCLUSION: When symptoms increase, therapists for individuals with APS should be attentive to potential disruptions in WA, though strong WA may be a cross-sectional protective factor.

Using search engine data to gauge public interest in mental health, politics and violence in the context of mass shootings.

Despite significant potential for providing insight to private perceptions and behaviors, search engine data has yet to be utilized as a means of gauging the U.S. public's interest and understanding of mental health in the context of gun violence and politics. An analysis of Google Trends revealed that Mental health searches increased in volume starting in the beginning of the current decade. Notably, both "mental health" and "gun(s)" were searched with greater frequency the week after the mass shooting events occurred. Related searches after the event also observed a significant increase in interest in mental health and gun regulation, legal reform, mass shootings, and gun(s). Results suggest that the American public's perception of mental illness increasingly incorporates associations with themes of violence and politics, which becomes more apparent surrounding mass shooting events. Future studies are needed to determine implications for stigmatization of vulnerable groups, and possible relations to media coverage.

Machine learning algorithms can classify outdoor terrain types during running using accelerometry data.

BACKGROUND: Running is a popular physical activity that benefits health; however, running surface characteristics may influence loading impact and injury risk. Machine learning algorithms could automatically identify running surface from wearable motion sensors to quantify running exposures, and perhaps loading and injury risk for a runner. RESEARCH QUESTION: (1) How accurately can machine learning algorithms identify surface type from three-dimensional accelerometer sensors? (2) Does the sensor count (single or two-sensor setup) affect model accuracy? METHODS: Twenty-nine healthy adults (23.3 ±â€¯3.6 years, 1.8 ±â€¯0.1 m, and 63.6 ±â€¯8.5 kg) participated in this study. Participants ran on three different surfaces (concrete, synthetic, woodchip) while fit with two three-dimensional accelerometers (lower-back and right tibia). Summary features (n = 208) were extracted from the accelerometer signals. Feature-based Gradient Boosting (GB) and signal-based deep learning Convolutional Neural Network (CNN) models were developed. Models were trained on 90% of the data and tested on the remaining 10%. The process was repeated five times, with data randomly shuffled between train-test splits, to quantify model performance variability. RESULTS: All models and configurations achieved greater than 90% average accuracy. The highest performing models were the two-sensor GB and tibia-sensor CNN (average accuracy of 97.0 ±â€¯0.7 and 96.1 ±â€¯2.6%, respectively). SIGNIFICANCE: Machine learning algorithms trained on running data from a single- or dual-sensor accelerometer setup can accurately distinguish between surfaces types. Automatic identification of surfaces encountered during running activities could help runners and coaches better monitor training load, improve performance, and reduce injury rates.

Effect of walking surface, late-cueing, physiological characteristics of aging, and gait parameters on turn style preference in healthy, older adults.

Turning while walking is a crucial component of locomotion, often performed on irregular surfaces with little planning time. Turns can be difficult for some older adults due to physiological age-related changes. Two different turning strategies have been identified in the literature. During step turns, which are biomechanically stable, the body rotates about the outside limb, while for spin turns, generally performed with closer foot-to-foot distance, the inside limb is the main pivot point. Turning strategy preferences of older adults under challenging conditions remains unclear. The aim of this study was to determine how turning strategy preference in healthy older adults is modulated by surface features, cueing time, physiological characteristics of aging, and gait parameters. Seventeen healthy older adults (71.5 ±â€¯4.2 years) performed 90° turns for two surfaces (flat, uneven) and two cue conditions (pre-planned, late-cue). Gait parameters were identified from kinematic data. Measures of lower-limb strength, balance, and reaction-time were also recorded. Generalized linear (logistic) regression mixed-effects models examined the effect of (1) surface and cuing, (2) physiological characteristics of ageing, and (3) gait parameters on turn strategy preference. Step turns were preferred when the condition was pre-planned (p < 0.001) (model 1) and when the gait parameters of stride regularity and maximum acceleration decreased (p = 0.010 and p = 0.039, respectively) (model 3). Differences in turn strategy selection under dynamic conditions ought to be evaluated in future fall-risk research and rehabilitation utilizing real-world activity monitoring.

Aging may negatively impact movement smoothness during stair negotiation.

Stairs represent a barrier to safe locomotion for some older adults, potentially leading to the adoption of a cautious gait strategy that may lack fluidity. This strategy may be characterized as unsmooth; however, stair negotiation smoothness has yet to be quantified. The aims of this study were to assess age- and task-related differences in head and body center of mass (COM) acceleration patterns and smoothness during stair negotiation and to determine if smoothness was associated with the timed "Up and Go" (TUG) test of functional movement. Motion data from nineteen older and twenty young adults performing stair ascent, stair descent, and overground straight walking trials were analyzed and used to compute smoothness based on the log-normalized dimensionless jerk (LDJ) and the velocity spectral arc length (SPARC) metrics. The associations between TUG and smoothness measures were evaluated using Pearson's correlation coefficient (r). Stair tasks increased head and body COM acceleration pattern differences across groups, compared to walking (p < 0.05). LDJ smoothness for the head and body COM decreased in older adults during stair descent, compared to young adults (p ≤ 0.015) and worsened with increasing TUG for all tasks (-0.60 ≤ r ≤ -0.43). SPARC smoothness of the head and body COM increased in older adults, regardless of task (p < 0.001), while correlations showed improved SPARC smoothness with increasing TUG for some tasks (0.33 ≤ r ≤ 0.40). The LDJ outperforms SPARC in identifying age-related stair negotiation adaptations and is associated with performance on a clinical test of gait.

Machine learning algorithms based on signals from a single wearable inertial sensor can detect surface- and age-related differences in walking.

The aim of this study was to investigate if a machine learning algorithm utilizing triaxial accelerometer, gyroscope, and magnetometer data from an inertial motion unit (IMU) could detect surface- and age-related differences in walking. Seventeen older (71.5 ±â€¯4.2 years) and eighteen young (27.0 ±â€¯4.7 years) healthy adults walked over flat and uneven brick surfaces wearing an inertial measurement unit (IMU) over the L5 vertebra. IMU data were binned into smaller data segments using 4-s sliding windows with 1-s step lengths. Ninety percent of the data were used as training inputs and the remaining ten percent were saved for testing. A deep learning network with long short-term memory units was used for training (fully supervised), prediction, and implementation. Four models were trained using the following inputs: all nine channels from every sensor in the IMU (fully trained model), accelerometer signals alone, gyroscope signals alone, and magnetometer signals alone. The fully trained models for surface and age outperformed all other models (area under the receiver operator curve, AUC = 0.97 and 0.96, respectively; p ≤ .045). The fully trained models for surface and age had high accuracy (96.3, 94.7%), precision (96.4, 95.2%), recall (96.3, 94.7%), and f1-score (96.3, 94.6%). These results demonstrate that processing the signals of a single IMU device with machine-learning algorithms enables the detection of surface conditions and age-group status from an individual's walking behavior which, with further learning, may be utilized to facilitate identifying and intervening on fall risk.

Gait adaptations of older adults on an uneven brick surface can be predicted by age-related physiological changes in strength.

BACKGROUND: Outdoor falls in community-dwelling older adults are often triggered by uneven pedestrian walkways. It remains unclear how older adults adapt to uneven surfaces typically encountered in the outdoor built-environment and whether these adaptations are associated to age-related physiological changes. RESEARCH QUESTION: The aims of this study were to (1) compare gait parameters over uneven and flat brick walkways, (2) evaluate the differences between older and young adults for these two surfaces, and (3) assess if physiological characteristics could predict adaptations in older adults. METHODS: Balance, strength, reaction-time, full-body marker positions, and acceleration signals from a trunk-mounted inertial measurement unit were collected in seventeen older (71.5 ±â€¯4.2 years) and eighteen young (27.0 ±â€¯4.7 years) healthy adults to compute lower-limb joint kinematics, spatio-temporal parameters, dynamic stability, and accelerometry-derived metrics (symmetry, consistency, and smoothness). RESULTS: Both groups increased hip flexion at foot-strike, while decreasing ankle dorsiflexion, margin of stability, symmetry, and consistency on the uneven, compared to flat, surface. Older, compared to young, adults showed a larger increase in knee flexion at foot-strike and a larger decrease in smoothness on the uneven surface. Only young adults decreased hip abduction on the uneven surface. Strength, not balance nor reaction-time, was the main predictor of hip abduction in older adults on both surfaces. SIGNIFICANCE: While older adults may be especially vulnerable, uneven surfaces negatively impact gait, irrespective of age, and could represent a risk to all pedestrians.

Soldier-relevant body borne load impacts minimum foot clearance during obstacle negotiation.

Soldiers often trip and fall on duty, resulting in injury. This study examined ten male soldiers' ability to negotiate an obstacle. Participants had lead and trail foot minimum foot clearance (MFC) parameters quantified while crossing a low (305 mm) and high (457 mm) obstacle with (19.4 kg) and without (6 kg) body borne load. To minimize tripping risk, participants increased lead foot MFC (p = 0.028) and reduced lead (p = 0.044) and trail (p = 0.035) foot variability when negotiating an obstacle with body borne load. While obstacle height had no effect on MFC (p = 0.273 and p = 0.126), placing the trail foot closer to the high obstacle when crossing with body borne load, resulted in greater lead (R = 0.640, b = 0.241, p = 0.046) and trail (R = 0.636, b = 0.287, p = 0.048) MFC. Soldiers, when carrying typical military loads, may be able to minimize their risk of tripping over an obstacle by creating a safety margin via greater foot clearance with reduced variability.

Lower limb flexion posture relates to energy absorption during drop landings with soldier-relevant body borne loads.

Fifteen military personnel performed 30-cm drop landings to quantify how body borne load (light, ∼6 kg, medium, ∼20 kg, and heavy, ∼40 kg) impacts lower limb kinematics and knee joint energy absorption during landing, and determine whether greater lower limb flexion increases energy absorption while landing with load. Participants decreased peak hip (P = 0.002), and knee flexion (P = 0.007) posture, but did not increase hip (P = 0.796), knee (P = 0.427) or ankle (P = 0.161) energy absorption, despite exhibiting greater peak hip (P = 0.003) and knee (P = 0.001) flexion, and ankle (P = 0.003) dorsiflexion angular impulse when landing with additional load. Yet, when landing with the light and medium loads, greater hip (R(2) = 0.500, P = 0.003 and R(2) = 0.314, P = 0.030) and knee (R(2) = 0.431, P = 0.008 and R(2) = 0.342, P = 0.022) flexion posture predicted larger knee joint energy absorption. Thus, military training that promotes hip and knee flexion, and subsequently greater energy absorption during landing, may potentially reduce risk of musculoskeletal injury and optimize soldier performance.

Canine urothelial carcinoma: genomically aberrant and comparatively relevant.

Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 % and 84 % of cases, respectively, and losses on CFA 19 were present in 77 % of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications.

Body borne loads impact walk-to-run and running biomechanics.

The purpose of this study was to perform a biomechanics-based assessment of body borne load during the walk-to-run transition and steady-state running because historical research has limited load carriage assessment to prolonged walking. Fifteen male military personnel had trunk and lower limb biomechanics examined during these locomotor tasks with three different load configurations (light, ∼6 kg, medium, ∼20 kg, and heavy, ∼40 kg). Subject-based means of the dependent variables were submitted to repeated measures ANOVA to test the effects of load configuration. During the walk-to-run transition, the hip decreased (P=0.001) and knee increased (P=0.004) their contribution to joint power with the addition of load. Additionally, greater peak trunk (P=0.001), hip (P=0.001), and knee flexion (P<0.001) moments and trunk flexion (P<0.001) angle, and reduced hip (P=0.001) and knee flexion (P=0.001) posture were evident during the loaded walk-to-run transition. Body borne load had no significant effect (P>0.05) on distribution of lower limb joint power during steady-state running, but increased peak trunk (P<0.001), hip (P=0.001), and knee (P=0.001) flexion moments, and trunk flexion (P<0.001) posture were evident. During the walk-to-run transition the load carrier may move joint power production distally down the kinetic chain and adopt biomechanical profiles to maintain performance of the task. The load carrier, however, may not adopt lower limb kinematic adaptations necessary to shift joint power distribution during steady-state running, despite exhibiting potentially detrimental larger lower limb joint loads. As such, further study appears needed to determine how load carriage impairs maximal locomotor performance.

A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors.

The aim of this study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of E7107 in patients with advanced solid tumors. Patients in this phase I, open-label, single-arm, dose-escalation study had metastatic or locally advanced solid tumors and received E7107 as a 30-minute intravenous infusion at doses of 0.6, 1.2, 1.8, 2.4, 3.2, 4.3, and 5.7 mg/m(2). Twenty-six patients were enrolled in the study. At 5.7 mg/m(2), two patients experienced dose-limiting toxicities including diarrhea, vomiting, dehydration, and myocardial infarction on Days 1-3 following E7107 administration. Three additional patients were recruited at the lower dose and all six patients tolerated E7107 4.3 mg/m(2) with no dose-limiting toxicities. The maximum tolerated dose of E7107 was therefore 4.3 mg/m(2). The most common drug-related adverse events were nausea, vomiting, and diarrhea. Vision loss was experienced by two patients at Cycles 2 and 7, each patient receiving 3.2 mg/m(2) and 4.3 mg/m(2), respectively. This resulted in the study being put on clinical hold. Pharmacokinetic analysis showed that E7107 was rapidly distributed with a moderate elimination half-life (6-13 h) and high clearance. Exposure to E7107 was dose-related. The best tumor response was stable disease in eight patients. E7107 is a unique first-in-class molecule. The incidence of two cases of vision loss probably related to E7107 led to study discontinuation.

Shared acquired genomic changes in zebrafish and human T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging clinical entity with high rates of induction failure and relapse. To discover the genetic changes occurring in T-ALL, and those contributing to relapse, we studied zebrafish (Danio rerio) T-ALL samples using array comparative genomic hybridization (aCGH). We performed aCGH on 17 T-ALLs from four zebrafish T-ALL models, and evaluated similarities between fish and humans by comparing all D. rerio genes with copy number aberrations (CNAs) with a cohort of 75 published human T-ALLs analyzed by aCGH. Within all D. rerio CNAs, we identified 893 genes with human homologues and found significant overlap (67%) with the human CNA dataset. In addition, when we restricted our analysis to primary T-ALLs (14 zebrafish and 61 human samples), 10 genes were recurrently altered in > 3 zebrafish cancers and ≥ 4 human cases, suggesting a conserved role for these loci in T-ALL transformation across species. We also conducted iterative allo-transplantation with three zebrafish malignancies. This technique selects for aggressive disease, resulting in shorter survival times in successive transplant rounds and modeling refractory and relapsed human T-ALL. Fifty-five percent of original CNAs were preserved after serial transplantation, demonstrating clonality between each primary and passaged leukemia. Cancers acquired an average of 34 new CNAs during passaging. Genes in these loci may underlie the enhanced malignant behavior of these neoplasias. We also compared genes from CNAs of passaged zebrafish malignancies with aCGH results from 50 human T-ALL patients who failed induction, relapsed or would eventually relapse. Again, many genes (88/164) were shared by both datasets. Further, nine recurrently altered genes in passaged D. rerio T-ALL were also found in multiple human T-ALL cases. These results suggest that zebrafish and human T-ALLs are similar at the genomic level, and are governed by factors that have persisted throughout evolution.

Recent advances in the molecular pathogenesis of Ewing's sarcoma.

Tumor development is a complex process resulting from interplay between mutations in oncogenes and tumor suppressors, host susceptibility factors, and cellular context. Great advances have been made by studying rare tumors with unique clinical, genetic, or molecular features. Ewing's sarcoma serves as an excellent paradigm for understanding tumorigenesis because it exhibits some very useful and important characteristics. For example, nearly all cases of Ewing's sarcoma contain the (11;22)(q24;q12) chromosomal translocation that encodes the EWS/FLI oncoprotein. Besides the t(11;22), however, many cases have otherwise simple karyotypes with no other demonstrable abnormalities. Furthermore, it seems that an underlying genetic susceptibility to Ewing's sarcoma, if it exists, must be rare. These two features suggest that EWS/FLI is the primary mutation that drives the development of this tumor. Finally, Ewing's sarcoma is an aggressive tumor that requires aggressive treatment. Thus, improved understanding of the pathogenesis of this tumor will not only be of academic interest, but may also lead to new therapeutic approaches for individuals afflicted with this disease. The purpose of this review is to highlight recent advances in understanding the molecular pathogenesis of Ewing's sarcoma, while considering the questions surrounding this disease that still remain and how this knowledge may be applied to developing new treatments for patients with this highly aggressive disease.

Is There a Predisposition Gene for Ewing's Sarcoma?

Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma.

Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls.

Archived neonatal blood cards (Guthrie cards) from children who later contracted leukaemia and matched normal controls were assayed for adenovirus (AdV) C DNA content using two highly sensitive methods. In contrast to a previous report, AdV DNA was not detected at a higher frequency among neonates who later developed leukaemia, when compared with controls.

Controllable formation of nanoscale patterns on TiO2 by conductive-AFM nanolithography.

We report on the nanopatterning of double-bond-terminated silane (5-hexenyltrichlorosilane, HTCS) molecules on titania (TiO2) using conductive atomic force microscopy (AFM). The influences of tip electrostatic potential and scanning velocity, relative humidity and of the repeated application of voltage on the topographic height, width, and hydrophilic and hydrophobic contrast of the resultant patterns were investigated. Tip voltage and tip velocity ( v) were applied between -10 V

Progressive outer retinal necrosis presenting with isolated optic neuropathy.

Progressive outer retinal necrosis is a necrotizing herpetic retinopathy usually seen in immunocompromised patients. The authors describe two patients with this disease who initially had findings suggestive of an optic neuropathy. Vision declined after treatment with methylprednisolone, after which fundus examination became consistent with progressive outer retinal necrosis. These cases underscore the importance of careful examination of the retinal periphery before management of any presumed optic neuropathy with steroids.