Effects of temperature on viral load, inclusion body formation, and host response in Pacific Herring with viral erythrocytic necrosis (VEN).

OBJECTIVE: The primary objective of this study was to determine the effects of temperature on viral erythrocytic necrosis (VEN) progression under controlled conditions. Secondarily, this study was intended to evaluate the combined effects of temperature and VEN on the Pacific Herring Clupea palasii transcriptome. METHODS: The effects of temperature on VEN progression were assessed by waterborne exposure of laboratory-reared, specific-pathogen-free Pacific Herring to tissues homogenates containing erythrocytic necrosis virus (ENV) at 6.9, 9.0, or 13.5°C. RESULT: Exposure of Pacific Herring to ENV resulted in the establishment of infections characterized by high infection prevalence (89%; 40/45) and mean viral loads (5.5 log10 [gene copies/µg genomic DNA]) in kidney tissues at 44 days postexposure. Mean viral loads were significantly higher in fish from the ambient (mean = 9.0°C) and warm (mean = 13.5°C) treatments (6.1-6.2 log10 [gene copies/total genomic DNA]) than in fish from the cool (mean = 6.9°C) treatment (4.3 log10 [gene copies/µg genomic DNA]). Similarly, the peak proportion of diseased fish was directly related to temperature, with cytoplasmic inclusion bodies detected in 21% of fish from the cool treatment, 52% of fish from the ambient treatment, and 60% of fish from the warm treatment. The mean VEN load in each fish (enumerated as the percentage of erythrocytes with cytoplasmic inclusions) at 44 days postexposure increased with temperature from 15% in the cool treatment to 36% in the ambient treatment and 32% in the warm treatment. Transcriptional analysis indicated that the number of differentially expressed genes among ENV-exposed Pacific Herring increased with temperature, time postexposure, and viral load. Correlation network analysis of transcriptomic data showed robust activation of interferon and viral immune responses in the hepatic tissue of infected individuals independent of other experimental variables. CONCLUSION: Results from this controlled laboratory study, combined with previous observations of natural epizootics in wild populations, support the conclusion that temperature is an important disease cofactor for VEN in Pacific Herring.

HLA and amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with loss of upper and lower motor neurones. It leads to death by respiratory failure and has a typical prognosis of 2-3 years. The immune system has been shown to play a role in the pathophysiology of ALS. Some of the most important immune genes are within the human leukocyte antigen (HLA) region, and a recent genome-wide association study (GWAS) has identified a risk allele for ALS within the HLA region. Older studies have also suggested an HLA association with ALS, with certain HLA alleles showing differing expression between patients and controls. This systematic review and meta-analysis examines the previous studies performed in this field.Methods: We used established publication search engines. Findings were excluded if they did not meet the selection criteria. We then undertook statistical meta-analysis on the eligible papers, using a fixed effects model.Results: There were eight eligible papers. There were three statistically significant meta-analysis findings, although these would not be significant after correction for multiple comparisons. The frequencies of HLA-A9 and HLA-DR4 genotypes were lower in ALS subjects than controls, and HLA-B35 was higher in ALS subjects.Discussion: This systematic review and meta-analysis do not confirm all the previously reported associations of HLA with ALS, but shows three alleles of interest. However, there are limitations to the studies, which include the use of older serotyping methodology and the small numbers of subjects. Given the recent GWAS association with HLA, further modern HLA studies are warranted.

Perceptions of autism spectrum disorder among the Swahili community on the Kenyan coast.

BACKGROUND: In high-income and Western societies there is great understanding and awareness of autism spectrum disorder (ASD); however, for many low-middle income countries, research and knowledge is notably lacking. In Africa, there is a growing prevalence of ASD due to increased diagnosis, yet it is still a poorly understood condition. AIMS: Emerging literature has emphasised how cultural and societal beliefs underpin the level of understanding of ASD, and which typically results in lack of awareness and acceptance. As such it is important to investigate the cultural perceptions towards ASD within low-middle income communities of African culture, to further understand the challenges and barriers individuals with ASD face. The aim of the current study was to probe participants from the Swahili community, on the coast of Kenya, of their cultural views towards ASD. METHOD: Semi-structured interviews were conducted with seven participants, and the data analysed using thematic analysis. RESULTS: Three key themes developed from the data; stigma, lack of awareness, and Government responsibility. CONCLUSION: Cultural perceptions negatively impacted awareness and are exacerbated by lack of directive from the Government in providing appropriate diagnostic and educational support.

In the temporal organization of episodic memory, the hippocampus supports the experience of elapsed time.

Space and time are both essential features of episodic memory, for which the hippocampus is critical (Howard & Eichenbaum, 2015). Spatial tasks have been used effectively to study the behavioral relevance of place cells. However, the behavioral paradigms utilized for the study of time cells have not used time duration as a variable that animals need to be aware of to solve the task. Therefore, the behavioral relevance of this cell firing is unclear. In order to directly study the role of the hippocampus in processing elapsed time, we created a novel time duration discrimination task. Rats learned to make a decision to turn left or right depending on the preceding tone duration (10 s, left turn; 20 s, right turn). Once the rats reached criterion performance of 90% correct on two out of three consecutive days, they received either an excitotoxic hippocampal lesion or a sham-lesion surgery. After recovery, rats were tested to determine hippocampal involvement in discriminating time duration. Rats with hippocampal lesions performed at chance level on their first testing day postlesion, and they were impaired relative to the sham-lesioned rats. Although the hippocampal-lesioned rats began discriminating at above chance level, their performance never returned to criterion even with 50 days of postoperative testing. Furthermore, while sham rats showed no difference in the number of errors they made on 10- versus 20-s delay trials, hippocampal lesion rats similarly improved their performance under the 10-s delay condition, but not under the 20-s delay condition. Results indicate that hippocampal lesions resulted in a selective impairment in discriminating elapsed time only during the longer delay trials. The implications of these results are discussed in relation to the limits of working-memory capacity and to the role of sustained hippocampal time cell activity in memory performance depending on the perceived relevance of the delay period.

Ampakines stimulate phrenic motor output after cervical spinal cord injury.

Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors increases phrenic motor output. Ampakines are a class of drugs that are positive allosteric modulators of AMPA receptors. We hypothesized that 1) ampakines can stimulate phrenic activity after incomplete cervical spinal cord injury (SCI), and 2) pairing ampakines with brief hypoxia could enable sustained facilitation of phrenic bursting. Phrenic activity was recorded ipsilateral (IL) and contralateral (CL) to C2 spinal cord hemisection (C2Hx) in anesthetized adult rats. Two weeks after C2Hx, ampakine CX717 (15 mg/kg, i.v.) increased IL (61 ± 46% baseline, BL) and CL burst amplitude (47 ± 26%BL) in 8 of 8 rats. After 90 min, IL and CL bursting remained above baseline (BL) in 7 of 8 rats. Pairing ampakine with a single bout of acute hypoxia (5-min, arterial partial pressure of O2 ~ 50 mmHg) had a variable impact on phrenic bursting, with some rats showing a large facilitation that exceeded the response of the ampakine alone group. At 8 weeks post-C2Hx, 7 of 8 rats increased IL (115 ± 117%BL) and CL burst amplitude (45 ± 27%BL) after ampakine. The IL burst amplitude remained above BL for 90-min in 7 of 8 rats; CL bursting remained elevated in 6 of 8 rats. The sustained impact of ampakine at 8 weeks was not enhanced by hypoxia exposure. Intravenous vehicle (10% 2-Hydroxypropyl-ß-cyclodextrin) did not increase phrenic bursting at either time point. We conclude that ampakines effectively stimulate neural drive to the diaphragm after cervical SCI. Pairing ampakines with a single hypoxic exposure did not consistently enhance phrenic motor facilitation.

Differential effects of an electronic symptom monitoring intervention based on the age of patients with advanced cancer.

BACKGROUND: Symptom monitoring interventions enhance patient outcomes, including quality of life (QoL), health care utilization, and survival, but it remains unclear whether older and younger patients with cancer derive similar benefits. We explored whether age moderates the improved outcomes seen with an outpatient electronic symptom monitoring intervention. PATIENTS AND METHODS: We carried out a secondary analysis of data from a randomized trial of 766 patients receiving chemotherapy for metastatic solid tumors. Patients received an electronic symptom monitoring intervention integrated with oncology care or usual oncology care alone. The intervention consisted of patients reporting their symptoms, which were provided to their physicians at clinic visits, and nurses receiving alerts for severe/worsening symptoms. We used regression models to determine whether age (older or younger than 70 years) moderated the effects of the intervention on QoL (EuroQol EQ-5D), emergency room (ER) visits, hospitalizations, and survival outcomes. RESULTS: Enrollment rates for younger (589/777 = 75.8%) and older (177/230 = 77.0%) patients did not differ. Older patients (median age = 75 years, range 70-91 years) were more likely to have an education level of high school or less (26.6% versus 20.9%, P = 0.029) and to be computer inexperienced (50.3% versus 23.4%, P < 0.001) compared with younger patients (median age = 58 years, range 26-69 years). Younger patients receiving the symptom monitoring intervention experienced lower risk of ER visits [hazard ratio (HR) = 0.74, P = 0.011] and improved survival (HR = 0.76, P = 0.011) compared with younger patients receiving usual care. However, older patients did not experience significantly lower risk of ER visits (HR = 0.90, P = 0.613) or improved survival (HR = 1.06, P = 0.753) with the intervention. We found no moderation effects based on age for QoL and risk of hospitalizations. CONCLUSIONS: Among patients with advanced cancer, age moderated the effects of an electronic symptom monitoring intervention on the risk of ER visits and survival, but not QoL. Symptom monitoring interventions may need to be tailored to the unique needs of older adults with cancer.

Pilot randomized trial of an electronic symptom monitoring intervention for hospitalized patients with cancer.

BACKGROUND: Hospitalized patients with cancer experience a high symptom burden, which is associated with poor health outcomes and increased health care utilization. However, studies investigating symptom monitoring interventions in this population are lacking. We conducted a pilot randomized trial to assess the feasibility and preliminary efficacy of a symptom monitoring intervention to improve symptom management in hospitalized patients with advanced cancer. PATIENTS AND METHODS: We randomly assigned patients with advanced cancer who were admitted to the inpatient oncology service to a symptom monitoring intervention or usual care. Patients in both arms self-reported their symptoms daily (Edmonton Symptom Assessment System and Patient Health Questionnaire-4). Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily team rounds. The primary end point of the study was feasibility. We defined the intervention as feasible if >75% of participants hospitalized >2 days completed >2 symptom reports. We observed daily rounds to determine whether clinicians discussed and developed a plan to address patients' symptoms. We used regression models to assess intervention effects on patients' symptoms throughout their hospitalization, readmission risk, and hospital length of stay (LOS). RESULTS: Among 150 enrolled patients (81.1% enrollment), 94.2% completed >2 symptom reports. Clinicians discussed 60.4% of the symptom reports and developed a plan to address the symptoms highlighted by the symptom reports 20.8% of the time. Compared with usual care, intervention patients had a greater proportion of days with lower psychological distress (B = 0.12, P = 0.008), but no significant difference in the proportion of days with improved Edmonton Symptom Assessment System-physical symptoms (B = 0.07, P = 0.138). Intervention patients had lower readmission risk (hazard ratio = 0.68, P = 0.224), although this difference was not significant. We found no significant intervention effects on hospital LOS (B = 0.16, P = 0.862). CONCLUSIONS: This symptom monitoring intervention is feasible and demonstrates encouraging preliminary efficacy for improving patients' symptoms and readmission risk.ClinicalTrials.gov identifier NCT02891993.

Evaluation of RIDA®GENE norovirus GI/GII real time RT-PCR using stool specimens collected from children and adults with acute gastroenteritis.

BACKGROUND: Norovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories. OBJECTIVE: To evaluate RIDA®GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE. STUDY DESIGN: Patients between 14 days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5'end of the norovirus ORF2 gene. RESULTS: A total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method. CONCLUSIONS: The RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE.

Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion.

BACKGROUND: The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician's decision-making process. OBJECTIVE: The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. METHODS: Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. RESULTS: Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. CONCLUSION: The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions.

An instrument to measure mechanical up-conversion phenomena in metals in the elastic regime.

Crystalline materials, such as metals, are known to exhibit deviation from a simple linear relation between strain and stress when the latter exceeds the yield stress. In addition, it has been shown that metals respond to varying external stress in a discontinuous way in this regime, exhibiting discrete releases of energy. This crackling noise has been extensively studied both experimentally and theoretically when the metals are operating in the plastic regime. In our study, we focus on the behavior of metals in the elastic regime, where the stresses are well below the yield stress. We describe an instrument that aims to characterize non-linear mechanical noise in metals when stressed in the elastic regime. In macroscopic systems, this phenomenon is expected to manifest as a non-stationary noise modulated by external disturbances applied to the material, a form of mechanical up-conversion of noise. The main motivation for this work is for the case of maraging steel components (cantilevers and wires) in the suspension systems of terrestrial gravitational wave detectors. Such instruments are planned to reach very ambitious displacement sensitivities, and therefore mechanical noise in the cantilevers could prove to be a limiting factor for the detectors' final sensitivities, mainly due to non-linear up-conversion of low frequency residual seismic motion to the frequencies of interest for the gravitational wave observations. We describe here the experimental setup, with a target sensitivity of 10(-15) m/Hz in the frequency range of 10-1000 Hz, a simple phenomenological model of the non-linear mechanical noise, and the analysis method that is inspired by this model.

Investigating a Novel Measure of Brain Networking Following Sports Concussion.

Clinicians managing sports-related concussions are left to their clinical judgment in making diagnoses and return-to-play decisions. This study was designed to evaluate the utility of a novel measure of functional brain networking for concussion management. 24 athletes with acutely diagnosed concussion and 21 control participants were evaluated in a research laboratory. At each of the 4 post-injury time points, participants completed the Axon assessment of neurocognitive function, a self-report symptom inventory, and the auditory oddball and go/no-go tasks while electroencephalogram (EEG) readings were recorded. Brain Network Activation (BNA) scores were calculated from EEG data related to the auditory oddball and go/no-go tasks. BNA scores were unable to differentiate between the concussed and control groups or by self-report symptom severity. These findings conflict with previous work implementing electrophysiological assessments in concussed athletes, suggesting that BNA requires additional investigation and refinement before clinical implementation.

Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation.

Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.

Factors associated with depression and anxiety symptoms in family caregivers of patients with incurable cancer.

BACKGROUND: Family caregivers (FCs) are critically important for patients with cancer, yet they may experience psychological distress related to caregiving demands. We sought to describe rates of depression and anxiety in FCs of patients with incurable cancer and identify factors associated with these symptoms to determine those at greatest risk for psychological distress. PATIENTS AND METHODS: We performed a cross-sectional analysis of baseline data from a randomized trial of early palliative care. We assessed depression and anxiety using the Hospital Anxiety and Depression Scale in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer and their FCs. We also assessed patients' quality of life (Functional Assessment of Cancer Therapy-General), coping strategies (Brief COPE), and their report of the primary goal of their cancer treatment. We used linear regression with purposeful selection of covariates to identify factors associated with FC depression and anxiety symptoms. RESULTS: We enrolled 78.6% (n = 275) of potentially eligible FCs. The majority were female (69.1%) and married to the patient (66.2%). While the proportion of FCs and patients reporting depression did not differ (16.4% versus 21.5%, P = 0.13), FCs were more likely to report anxiety compared with patients (42.2% versus 28.4%, P < 0.001). Patients' use of acceptance coping was associated with lower FC depression (B = -0.42, P < 0.001), while emotional support coping was associated with higher FC depression (B = 0.69, P = 0.001) and lower FC anxiety (B = -0.70, P < 0.001). Patient report that their primary goal of their treatment was to 'cure my cancer' was associated with higher FC depression (B = 0.72, P = 0.03). CONCLUSIONS: Patients with incurable cancer and their FCs report high levels of depression and anxiety symptoms. We demonstrated that patients' coping strategies and prognostic understanding were associated with FC depression and anxiety symptoms, underscoring the importance of targeting these risk factors when seeking to address the psychological distress experienced by FCs.

Insensitivity to Flaws Leads to Damage Tolerance in Brittle Architected Meta-Materials.

Cellular solids are instrumental in creating lightweight, strong, and damage-tolerant engineering materials. By extending feature size down to the nanoscale, we simultaneously exploit the architecture and material size effects to substantially enhance structural integrity of architected meta-materials. We discovered that hollow-tube alumina nanolattices with 3D kagome geometry that contained pre-fabricated flaws always failed at the same load as the pristine specimens when the ratio of notch length (a) to sample width (w) is no greater than 1/3, with no correlation between failure occurring at or away from the notch. Samples with (a/w) > 0.3, and notch length-to-unit cell size ratios of (a/l) > 5.2, failed at a lower peak loads because of the higher sample compliance when fewer unit cells span the intact region. Finite element simulations show that the failure is governed by purely tensile loading for (a/w) < 0.3 for the same (a/l); bending begins to play a significant role in failure as (a/w) increases. This experimental and computational work demonstrates that the discrete-continuum duality of architected structural meta-materials may give rise to their damage tolerance and insensitivity of failure to the presence of flaws even when made entirely of intrinsically brittle materials.

Recall of threat material is modulated by self or other referencing in people with high or low levels of non-clinical paranoia.

BACKGROUND AND OBJECTIVES: Biased processing of negatively valenced, and particularly threat-related material plays an important role in the development of paranoid thinking. This has been demonstrated by superior memory for threat-related information in patients with persecutory delusions and in non-clinical paranoia-prone participants. This study examined how emotional material was recalled having been encoded in relation to one self or to another person, in people high or low in paranoid ideation. It was predicted that people high in paranoia would recall more threat related material about others than people low in paranoia owing to being particularly alert to threats from other people. METHODS: Participants who reported high (N = 30) or low (N = 30) levels of sub-clinical paranoid thinking were presented with a series of threat-related and positive words and were asked to process them in terms of the self, or in terms of a fictional character. RESULTS: As predicted, when words were processed in terms of another person, the high paranoia group recalled more threat-related words than positive words, but when words had been processed in terms of the self, recall of threat-related and positive words did not differ. In contrast, there was no interaction between word-valence and referent in the low paranoia group. LIMITATIONS: These findings are drawn from an analogue sample. Replication in a sample of clinical participants who report persecutory delusions is required. CONCLUSIONS: People high in sub-clinical paranoid ideation recalled threat preferentially in relation to other people. Such information processing biases may help understand the development and maintenance of persecutory beliefs.

Industry-relevant magnetron sputtering and cathodic arc ultra-high vacuum deposition system for in situ x-ray diffraction studies of thin film growth using high energy synchrotron radiation.

We present an industry-relevant, large-scale, ultra-high vacuum (UHV) magnetron sputtering and cathodic arc deposition system purposefully designed for time-resolved in situ thin film deposition/annealing studies using high-energy (>50 keV), high photon flux (>10(12) ph/s) synchrotron radiation. The high photon flux, combined with a fast-acquisition-time (<1 s) two-dimensional (2D) detector, permits time-resolved in situ structural analysis of thin film formation processes. The high-energy synchrotron-radiation based x-rays result in small scattering angles (<11°), allowing large areas of reciprocal space to be imaged with a 2D detector. The system has been designed for use on the 1-tonne, ultra-high load, high-resolution hexapod at the P07 High Energy Materials Science beamline at PETRA III at the Deutsches Elektronen-Synchrotron in Hamburg, Germany. The deposition system includes standard features of a typical UHV deposition system plus a range of special features suited for synchrotron radiation studies and industry-relevant processes. We openly encourage the materials research community to contact us for collaborative opportunities using this unique and versatile scientific instrument.

Slip statistics of dislocation avalanches under different loading modes.

Slowly compressed microcrystals deform via intermittent slip events, observed as displacement jumps or stress drops. Experiments often use one of two loading modes: an increasing applied stress (stress driven, soft), or a constant strain rate (strain driven, hard). In this work we experimentally test the influence of the deformation loading conditions on the scaling behavior of slip events. It is found that these common deformation modes strongly affect time series properties, but not the scaling behavior of the slip statistics when analyzed with a mean-field model. With increasing plastic strain, the slip events are found to be smaller and more frequent when strain driven, and the slip-size distributions obtained for both drives collapse onto the same scaling function with the same exponents. The experimental results agree with the predictions of the used mean-field model, linking the slip behavior under different loading modes.

Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation.

Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants' prognostic understanding and asked the oncologists to estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30)) HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very' important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist (P<0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL (ß=-9.4, P=0.01) and greater depression at baseline (ß=1.7, P=0.02) and over time ((ß=1.2, P<0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support.

Independence of slip velocities on applied stress in small crystals.

Directly tracing the spatiotemporal dynamics of intermittent plasticity at the micro- and nanoscale reveals that the obtained slip dynamics are independent of applied stress over a range of up to ∼400 MPa, as well as being independent of plastic strain. Whilst this insensitivity to applied stress is unexpected for dislocation plasticity, the stress integrated statistical properties of both the slip size magnitude and the slip velocity follow known theoretical predictions for dislocation plasticity. Based on these findings, a link between the crystallographic slip velocities and an underlying dislocation avalanche velocity is proposed. Supporting dislocation dynamics simulations exhibit a similar regime during microplastic flow, where the mean dislocation velocity is insensitive to the applied stress. Combining both experimental and modeling observations, the results are discussed in a framework that firmly places the plasticity of nano- and micropillars in the microplastic regime of bulk crystals.