Comparison of neuromuscular fatigability amplitude and etiologies between fatigued and non-fatigued cancer patients.

PURPOSE: Cancer-related fatigue (CRF) is the most reported side effect of cancer and its treatments. Mechanisms of CRF are multidimensional, including neuromuscular alterations leading to decreased muscle strength and endurance (i.e., fatigability). Recently, exercise fatigability and CRF have been related, while fatigability mechanisms remain unclear. Traditionally, fatigability is assessed from maximal voluntary contractions (MVC) decrease, but some authors hypothesized that the rate of force development (RFD) determined during a rapid contraction could also be an interesting indicator of functional alterations. However, to our knowledge, no study investigated RFD in cancer patients. The purpose of this study was to determine whether RFD, fatigability amplitude, and etiology are different between fatigued and non-fatigued cancer patients. METHODS: Eighteen participants with cancer, divided in fatigued or non-fatigued groups according their CRF level, completed a 5-min all-out exercise in ankle plantar flexor muscles composed of 62 isometric MVC of 4 s with 1 s rest, to assess fatigability amplitude as the force-time relationship asymptote (FA). Before and after exercise, fatigability etiologies (i.e., voluntary activation (VA) and evoked forces by electrical stimulation (Db100)) were assessed as well as RFD in 50 and 100 ms (RFD50 and RFD100, respectively) during rapid contractions. RESULTS: FA is significantly lower in fatigued group. Significant differences were found between pre- and post-exercise VA, Db100, RFD50, and RFD100 for both groups, with no statistical difference between groups. CONCLUSION: During treatments, fatigability is higher in fatigued patients; however, the mechanisms of fatigability and RFD alterations are similar in both groups. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04391543, May 2020.

Advancing Naturalistic Affective Science with Deep Learning.

People express their own emotions and perceive others' emotions via a variety of channels, including facial movements, body gestures, vocal prosody, and language. Studying these channels of affective behavior offers insight into both the experience and perception of emotion. Prior research has predominantly focused on studying individual channels of affective behavior in isolation using tightly controlled, non-naturalistic experiments. This approach limits our understanding of emotion in more naturalistic contexts where different channels of information tend to interact. Traditional methods struggle to address this limitation: manually annotating behavior is time-consuming, making it infeasible to do at large scale; manually selecting and manipulating stimuli based on hypotheses may neglect unanticipated features, potentially generating biased conclusions; and common linear modeling approaches cannot fully capture the complex, nonlinear, and interactive nature of real-life affective processes. In this methodology review, we describe how deep learning can be applied to address these challenges to advance a more naturalistic affective science. First, we describe current practices in affective research and explain why existing methods face challenges in revealing a more naturalistic understanding of emotion. Second, we introduce deep learning approaches and explain how they can be applied to tackle three main challenges: quantifying naturalistic behaviors, selecting and manipulating naturalistic stimuli, and modeling naturalistic affective processes. Finally, we describe the limitations of these deep learning methods, and how these limitations might be avoided or mitigated. By detailing the promise and the peril of deep learning, this review aims to pave the way for a more naturalistic affective science.

Quantifying the reduction of airborne infectious viral load using a ventilated patient hood.

BACKGROUND: Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking. AIM: We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments. METHODS: We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer. FINDINGS: The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate. CONCLUSION: A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.

Distinct monitoring strategies underlie costs and performance in prospective memory.

Prospective memory (PM) describes the ability to remember to perform goal-relevant actions at an appropriate time in the future amid concurrent demands. A key contributor to PM performance is thought to be the effortful monitoring of the environment for PM-related cues, a process whose existence is typically inferred from a behavioral interference measure of reaction times. This measure, referred to as "PM costs," is an informative but indirect proxy for monitoring, and it may not be sufficient to understand PM behaviors in all situations. In this study, we asked participants to perform a visual search task with arrows that varied in difficulty while concurrently performing a delayed-recognition PM task with pictures of faces and scenes. To gain a precise measurement of monitoring behavior, we used eye-tracking to record fixations to all task-relevant stimuli and related these fixation measures to both PM costs and PM accuracy. We found that PM costs reflected dissociable monitoring strategies: higher costs were associated with early and frequent monitoring while lower costs were associated with delayed and infrequent monitoring. Moreover, the link between fixations and PM costs varied with cognitive load, and the inclusion of fixation data yielded better predictions of PM accuracy than using PM costs alone. This study demonstrates the benefit of eye-tracking to disentangle the nature of PM costs and more precisely describe strategies involved in prospective remembering.

Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. METHODS: BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. DISCUSSION: This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study.

PURPOSE: As a subjective symptom, cancer-related fatigue is assessed via patient-reported outcomes. Due to the inherent bias of such evaluation, screening and treatment for cancer-related fatigue remains suboptimal. The purpose is to evaluate whether objective cancer patients' hand muscle mechanical parameters (maximal force, critical force, force variability) extracted from a fatiguing handgrip exercise may be correlated to the different dimensions (physical, emotional, and cognitive) of cancer-related fatigue. METHODS: Fourteen women with advanced breast cancer, still under or having previously received chemotherapy within the preceding 3 months, and 11 healthy women participated to the present study. Cancer-related fatigue was first assessed through the EORTC QLQ-30 and its fatigue module. Fatigability was then measured during 60 maximal repeated handgrip contractions. The maximum force, critical force (asymptote of the force-time evolution), and force variability (root mean square of the successive differences) were extracted. Multiple regression models were performed to investigate the influence of the force parameters on cancer-related fatigue's dimensions. RESULTS: The multiple linear regression analysis evidenced that physical fatigue was best explained by maximum force and critical force (r = 0.81; p = 0.029). The emotional fatigue was best explained by maximum force, critical force, and force variability (r = 0.83; p = 0.008). The cognitive fatigue was best explained by critical force and force variability (r = 0.62; p = 0.035). CONCLUSION: The handgrip maximal force, critical force, and force variability may offer objective measures of the different dimensions of cancer-related fatigue and could provide a complementary approach to the patient reported outcomes.

Measuring the intensity of community programs and policies for preventing childhood obesity in a diverse sample of US communities: the Healthy Communities Study.

INTRODUCTION: Efforts to address the critical public health problem of childhood obesity are occurring across the USA; however, little is known about how to characterize the intensity of these efforts. OBJECTIVES: The purposes of this study are to describe the intensity of community programs and policies (CPPs) to address childhood obesity in 130 US communities and to examine the extent to which observed CPPs targeted multiple behaviours and employed a comprehensive array of strategies. METHODS: To document CPPs occurring over a 10-year period, key informants were interviewed using a semi-structured interview protocol. Staff coded CPPs for key characteristics related to intensity, including reach, duration and strategy. Three types of CPP scores were calculated for intensity of CPPs, targeting of CPPs towards multiple behaviours and strategies used. RESULTS: Nine thousand six hundred eighty-one CPPs were identified. On average, communities had 74 different CPPs in place (standard deviation 30), with variation in documented CPPs (range 25-295). Most communities experienced a steady, modest increase in intensity scores over 10 years. CPP targeting scores suggested that communities expanded the focus of their efforts over time to include more behaviours and strategies. CONCLUSIONS: Findings of this large-scale study indicate that great variation exists across communities in the intensity and focus of community interventions being implemented to address childhood obesity.

Body Perception and Action Following Deafness.

The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual capacities. We are only now starting to investigate how the deaf experience their own bodies and body-related abilities. Indeed, a growing corpus of research suggests that auditory input could play an important role in body-related processing. Deafness could therefore disturb such processes. It has also been suggested that many unexplained daily difficulties experienced by the deaf could be related to deficits in this underexplored field. In the present review, we propose an overview of the current state of knowledge on the effects of deafness on body-related processing.

Obesity is associated with prolonged activity of the quadriceps and gastrocnemii during gait.

PURPOSE: To examine the effect of obesity and its potential interaction with knee OA presence on the electromyography patterns of the major knee joint periarticular muscles during walking. SCOPE: One hundred and eighteen asymptomatic adults and 177 adults with moderate knee osteoarthritis were subdivided into categories of healthy weight (n = 77; 20 kg/m(2) < BMI < 25 kg/m(2)), overweight (n = 117; 25 kg/m(2) ⩽ BMI < 30 kg/m(2)), and obese (n = 101; BMI ⩾ 30 kg/m(2) based on their body mass index (BMI). All individuals underwent a three-dimensional gait analysis. Surface electromyograms from the lateral and medial gastrocnemii, lateral and medial hamstrings, vastus lateralis, vastus medialis, and rectus femoris were recorded during self-selected speed walking. Principal component analysis was used to extract major features of amplitude and temporal pattern variability from the electromyograms of each muscle group (gastrocnemii, quadriceps, hamstrings separately). Analysis of variance models tested for main BMI category effects and interaction effects for these features (α = 0.05). Statistically significant BMI category (i.e. obesity) effects were found for features that described more prolonged activations of the gastrocnemii and quadriceps muscles during the stance phase of gait with obesity (P < 0.05). CONCLUSIONS: Obesity was associated with prolonged activation of quadriceps and gastrocnemii, which can result in prolonged knee joint contact loading, and thereby may contribute to the predisposition of knee OA development and progression in obese individuals.

Introducing new vaccines in the poorest countries: what did we learn from the GAVI experience with financial sustainability?

This paper reviews the experience of the Global Alliance for Vaccines and Immunization (GAVI) in introducing hepatitis B and Haemophilus influenzae type b vaccines in the poorest countries, and explores how financing for immunization has changed since GAVI Fund resources were made available during its first wave of support between 2000 and 2006. The analysis of Financial Sustainability Plans in 50 countries allowed for some of the original funding assumptions of the GAVI approach to be tested against the realities in a wide set of countries, and to highlight implications for future immunization efforts. While the initial GAVI experience with financial sustainability has proved successful through the development of plans, and many countries have been able to both introduce new vaccines and mobilize additional financing for immunization, for future GAVI supported vaccine introduction, some country co-financing of these will be needed upfront for the approach to be more sustainable.

The carboxylation efficiency of the vitamin K-dependent clotting factors: studies with factor IX.

Haemophilia B is characterized by a deficiency of the gamma-carboxylated protein, factor IX (FIX). As a first step to optimize a gene therapy strategy to treat haemophilia B, we employed a previously described approach (Biochemistry 2000;39: 14322) of altering the propeptide of vitamin K-dependent proteins in vitro, to improve the carboxylation efficiency of FIX. Both native FIX and FIX with a prothrombin propeptide (proPT-FIX) produced recombinant FIX in vitro following transfection of their cDNAs into human embryonic kidney (HEK) 293 cells. Using hydroxyapatite chromatography to separate carboxylated from uncarboxylated FIX, we are able to show that >90% of FIX is gamma-carboxylated and that substituting the propeptide of prothrombin into FIX does not further increase the relative amounts of carboxylated material. These results demonstrate that the nature of the propeptide, per se is not the sole determinant of optimal carboxylation of FIX in our expression system in HEK 293 cells.

Oblique incidence reflection imaging of live cells: improving contrast and image quality with an objective mask.

Dry 40x and 60x microscope objectives were fitted with opaque black masks in order to eliminate reflection and scattering of light off the objective front lens assembly during oblique incidence reflection (OIR) microscopy. The reflection and scattering are shown to induce background glare that leads to degradation in the quality of the OIR images. Mask prototypes were designed and machined to snap onto the spring-loaded retractable front lens assembly of each objective. OIR images of live cells and normalized intensity line profiles are used to demonstrate that, if these alterations to the housing of the objective are implemented, background glare is significantly reduced with the 60x objective, and virtually eliminated with the 40x objective.

Neuromuscular alterations during walking in persons with moderate knee osteoarthritis.

This paper compared the neuromuscular responses during walking between those with early-stage knee osteoarthritis (OA) to asymptomatic controls. The rationale for studying those with mild to moderate knee OA was to determine the alterations in response to dynamic loading that might be expected before severe pain, joint space narrowing and joint surface changes occur. We used pattern recognition techniques to explore both amplitude and shape changes of the surface electromyograms recorded from seven muscles crossing the knee joint of 40 subjects with knee OA and 38 asymptomatic controls during a walking task. The principal patterns for each muscle grouping explained over 83% of the variance in the waveforms. This result supported the notion that the main neuromuscular patterns were similar between asymptomatic controls and those with OA, reflecting the specific roles of the major muscles during walking. ANOVA revealed significant (p<0.05) differences in the principal pattern scores reflecting both amplitude and shape alterations in the OA group and among muscles. These differences captured subtle changes in the neuromuscular responses of the subjects with OA throughout different phases of the gait cycle and most likely reflected changes in the mechanical environment (joint loading, instability) and pain. The subjects with OA attempted to increase activity of the lateral sites and reduce activity in the medial sites, having minimal but prolonged activity during late stance. Therefore, alterations in neuromuscular responses were found even in this high functioning group with moderate knee OA.

Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives.

A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes.

Growth performance, carcass and pork quality of finisher pigs fed oat-based diets containing different levels of beta-glucans.

A study was undertaken to investigate the growth performance and carcass and meat quality of pigs (BW = 52 to 108 kg) fed oat-based (Avena sativa L.) diets containing four levels of mixed-linkage (1 --> 3), (1 --> 4)-beta-D-glucans. One hundred sixty pigs-80 barrows and 80 gilts (average starting BW = 52.7 kg)--were allocated to one of five diets: a wheat-barley-based control diet and four experimental diets. The groats of Marion, a covered oat, and OT789, a hulless oat, were used to formulate four isonitrogenous and isocaloric diets to achieve 4.1,3.3, 2.1, or 1.6% total /beta-glucans (as fed). Growth performance (daily gain and gain to feed ratio) was not affected (P > 0.05) by the different levels of beta-glucans. Carcass yield, although lower (P < or = 0.05) for pigs fed the control diet, was similar (P > 0.05) for pigs fed any of the experimental diets. Cutout yields were also alike (P > 0.05) across the five diets. Beta-glucan content had no effect (P > 0.05) on the longissimus muscle area, or, by and large, on the proportions of commercial cuts; the only exceptions were a commercial picnic from pigs fed the 2.1% diet lower (P < 0.05) relative to all other diets and a lower (P < 0.5) commercial loin from pigs fed diets 4.1 or 3.3% relative to the control diet. Furthermore, the relative proportions oftotal lean, total bone, and total dissectable fat in the four lean cuts (picnic, butt, loin, and ham) were not different (P > 0.05) among the five diets. For pigs fed 4.1% beta-glucans, the proportion of lean in each of the four major cuts was lower (P < 0.05). No differences (P > 0.05) associated with the level of beta-glucans were detected for either the initial or ultimate pH mean values, the subjective assessment of color or structure of the longissimus muscle, or the instrumentally measured color (L value). Similarly, drip loss was not influenced (P > 0.05) by the level of beta-glucans in the diets. Soluble protein did differ (P < 0.05) among the high- to low-beta-glucans diets. No differences (P > 0.05) associated with diets were found for fat hardness and shear values of grilled pork chops. Chemical fat of the longissimus muscle from pigs fed 4.1, 3.3, or 2.1% beta-glucans was lower (P < 0.05) compared to pigs fed the control or 1.6% beta-glucans diets. In summary, no evidence of detrimental effect of beta-glucans in oat-based diets, particularly at levels below 4%, was detected, lending support for the inclusion of oat into finisher diets.

A novel approach to grading pork carcasses: computer vision and ultrasound.

A Computer Vision System prototype for grading pork carcasses was developed at the Lacombe Research System. The system consists of two components: ultrasound imaging to scan a cross-section of the loin muscle and video imaging to capture two-dimensional (2D) and three-dimensional (3D) images of the carcass. For each of the 241 carcasses (114 barrows and 127 gilts), salable meat yield was determined from a full cutout. Linear, two- and three-dimensional, angular and curvature measurements and carcass volume were derived from each image. Muscle area and fat thickness (7 cm off the mid-line) measured by ultrasound at the next to last rib site, together with 2D and 3D measurements provided the most accurate model for estimating salable meat yield (R(2)=0.82 and RSD=1.68). Models incorporating fat thickness and muscle depth measured at the Canadian grading site (3/4 last rib, 7 cm off the mid-line) with the Destron PG-100 probe, had the lowest R(2) and highest residual standard deviation (RSD) values (R(2)=0.66 and RSD=2.15). Cross-validation demonstrated the reliability and stability of the models; hence conferring them good industry applicability. The Lacombe Computer Vision System prototype appears to offer a marked improvement over probes currently used by the Canadian pork industry.

How do mothers' childrearing histories, stress and parenting affect children's behavioural outcomes?

BACKGROUND: Information is needed to understand the role of low to moderate levels of mothers' emotional stress and child characteristics (i.e. prematurity) on parenting behaviours and their impact on children's behaviour that might be deemed 'challenging' but not 'disordered'. METHODS: The direct and indirect relations of maternal childrearing history and emotional stress, and observed parenting practices when children were 3 years of age on 4-year child behavioural outcomes was examined in a sample of low-income families with a term (n=112) or preterm (n=180) child. Parenting practices included displays of warmth and restrictiveness when interacting with their children. Child outcomes at 4 years included observation of social initiations with their mothers and maternal report of social and attentional problems. RESULTS: A Structural Equation Model building approach guided by specific hypotheses indicated that preterm as compared to full-term children had more maternal reported social and attentional problems but did not differ in observed social initiating skills. Greater negative maternal childrearing history indirectly influenced social initiating skills through its direct influence on maternal emotional stress. Greater maternal emotional stress directly influenced mothers' parenting that, in turn, directly influenced social initiating. Prematurity and a more negative childrearing history had a direct negative influence on the maternal report of social and attentional behavioural outcomes. CONCLUSIONS: These findings delineate the effects of prematurity and maternal parenting on the behaviour of 4-year-old-children and extend current knowledge of the influence of parental emotional stress on parenting. Even milder levels can negatively influence parenting, and in turn, contribute to children's less well developed social skills. The issues raised in this study could help with the identification and prioritization of medical and psychological services.

Modulation of breathing using imperceptible unloading.

We investigated the role of V(T) and V(T)/T(I) modulation of breathing in awake human subjects. We applied a PRBS of volume (incrementing ramp) or flow (decrementing wave) assist at levels below the perceptual threshold in order to stimulate respiratory feedback. We modeled the PRBS data with linear difference equations to obtain impulse-response profiles of V(T), V(T)/T(I), T(I) and factorial(P(MUS)). We limited cortical responses to our stimuli by applying sub-threshold levels of assist, and we limited humoral effects (O2 and CO2) by augmenting mechanical respiratory output intermittently and by small amounts. We found that flow or volume assist elicited similar significant increases in V(T) and V(T)/T(I). During flow assist there was a significant decrease in factorial(P(MUS)) and T(I) was reduced, albeit not significantly; however, volume assist did not modify T(I) or factorial(P(MUS)). The earlier onset of flow assist, relative to volume assist, may explain the difference between the responses. We conclude that vagally mediated inspiratory flow receptors in the chest wall or lungs may modulate breathing on a breath by breath basis when small, imperceptible increases in airflow occur early during inspiration. Furthermore, lung volume feedback during imperceptible unloading (occurring at the end of inspiration) was less effective. Finally, pseudorandom unloading with imperceptible stimuli provides a useful tool to study reflex regulation of ventilation in awake subjects without confounding cortical influences.

Sleep histories are seldom documented on a general medical service.

BACKGROUND: Sleep disorders are common, but the frequency of sleep history documentation in hospitalized patients is unknown. METHODS: We reviewed 442 initial histories and physical examinations recorded by 122 house officers and 47 medical students in 208 consecutive general medicine ward patients. RESULTS: Any reference to sleep was recorded in only 18 patients (9%), including 12 of 141 (9%) with conditions associated with obstructive sleep apnea. Sleep histories were recorded more often in women (13% vs 4%) and less often than histories of cigarette smoking or alcohol use. Medical students recorded such histories more often than did house officers. Patients with sleep histories more often had pulse oximetry (78% vs 37%), pulmonary function testing (11% vs 1%), arterial blood gas analysis (67% vs 30%), or electrocardiograms (78% vs 49%). CONCLUSIONS: Sleep histories are documented infrequently in hospitalized patients. Patients with a recorded sleep history more often have tests that suggest increased concerns about cardiorespiratory risk and/or a different process of care.