Elevated emotion network connectivity is associated with fluctuations in depression.

Elevated emotion network connectivity is thought to leave people vulnerable to become and stay depressed. The mechanism through which this arises is however unclear. Here, we test the idea that the connectivity of emotion networks is associated with more extreme fluctuations in depression over time, rather than necessarily more severe depression. We gathered data from two independent samples of N = 155 paid students and N = 194 citizen scientists who rated their positive and negative emotions on a smartphone app twice a day and completed a weekly depression questionnaire for 8 wk. We constructed thousands of personalized emotion networks for each participant and tested whether connectivity was associated with severity of depression or its variance over 8 wk. Network connectivity was positively associated with baseline depression severity in citizen scientists, but not paid students. In contrast, 8-wk variance of depression was correlated with network connectivity in both samples. When controlling for depression variance, the association between connectivity and baseline depression severity in citizen scientists was no longer significant. We replicated these findings in an independent community sample (N = 519). We conclude that elevated network connectivity is associated with greater variability in depression symptoms. This variability only translates into increased severity in samples where depression is on average low and positively skewed, causing mean and variance to be more strongly correlated. These findings, although correlational, suggest that while emotional network connectivity could predispose individuals to severe depression, it could also be leveraged to bring about therapeutic improvements.

Tuning the potency and selectivity of ImmTAC molecules by affinity modulation.

T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response. This class of bispecifics binds specific target peptides presented by human leukocyte antigen on the cell surface via an affinity-enhanced T-cell receptor and can redirect T-cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T-cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimizing the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proofreading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark state. These findings have important implications for the design of anti-CD3-based bispecifics with optimal biophysical parameters for both activity and specificity.

Rapid energy-efficient manufacturing of polymers and composites via frontal polymerization.

Thermoset polymers and composite materials are integral to today's aerospace, automotive, marine and energy industries and will be vital to the next generation of lightweight, energy-efficient structures in these enterprises, owing to their excellent specific stiffness and strength, thermal stability and chemical resistance1-5. The manufacture of high-performance thermoset components requires the monomer to be cured at high temperatures (around 180 °C) for several hours, under a combined external pressure and internal vacuum 6 . Curing is generally accomplished using large autoclaves or ovens that scale in size with the component. Hence this traditional curing approach is slow, requires a large amount of energy and involves substantial capital investment6,7. Frontal polymerization is a promising alternative curing strategy, in which a self-propagating exothermic reaction wave transforms liquid monomers to fully cured polymers. We report here the frontal polymerization of a high-performance thermoset polymer that allows the rapid fabrication of parts with microscale features, three-dimensional printed structures and carbon-fibre-reinforced polymer composites. Precise control of the polymerization kinetics at both ambient and elevated temperatures allows stable monomer solutions to transform into fully cured polymers within seconds, reducing energy requirements and cure times by several orders of magnitude compared with conventional oven or autoclave curing approaches. The resulting polymer and composite parts possess similar mechanical properties to those cured conventionally. This curing strategy greatly improves the efficiency of manufacturing of high-performance polymers and composites, and is widely applicable to many industries.

Connectome-based predictive modelling of cognitive reserve using task-based functional connectivity.

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modelling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.

Efficient free-space to on-chip coupling of THz-bandwidth pulses for biomolecule fingerprint sensing.

Wide bandwidth THz pulses can be used to record the distinctive spectral fingerprints related to the vibrational or rotational modes of polycrystalline biomolecules, and can be used to resolve the time-dependent dynamics of such systems. Waveguides, owing to their tight spatial confinement of the electromagnetic fields and the longer interaction distance, are promising platforms with which to study small volumes of such systems. The efficient input of sub-ps THz pulses into waveguides is challenging owing to the wide bandwidth of the THz signal. Here, we propose a sensing chip comprised of a pair of back-to-back Vivaldi antennas feeding into, and out from, a 90° bent slotline waveguide to overcome this problem. The effective operating bandwidth of the sensing chip ranges from 0.2 to 1.15 THz, and the free-space to on-chip coupling efficiency is as high as 51% at 0.44 THz. Over the entire band, the THz signal is ∼42 dB above the noise level at room temperature, with a peak of ∼73 dB above the noise. In order to demonstrate the use of the chip, we have measured the characteristic fingerprint of α-lactose monohydrate, and its sharp absorption peak at ∼0.53 THz was successfully observed, demonstrating the promise of our technique. The chip has the merits of efficient in-plane coupling, ultra-wide bandwidth, ease-of-integration, and simple fabrication. It has the potential for large-scale manufacture, and can be a strong candidate for integration into other THz light-matter interaction platforms.

An Accurate Millimeter-Wave Imaging Algorithm for Close-Range Monostatic System.

An efficient and more accurate millimeter-wave imaging algorithm, applied to a close-range monostatic personnel screening system, with consideration of dual path propagation loss, is presented in this paper. The algorithm is developed in accordance with a more rigorous physical model for the monostatic system. The physical model treats incident waves and scattered waves as spherical waves with a more rigorous amplitude term as per electromagnetic theory. As a result, the proposed method can achieve a better focusing effect for multiple targets in different range planes. Since the mathematical methods in classical algorithms, such as spherical wave decomposition and Weyl identity, cannot handle the corresponding mathematical model, the proposed algorithm is derived through the method of stationary phase (MSP). The algorithm has been validated by numerical simulations and laboratory experiments. Good performance in terms of computational efficiency and accuracy has been observed. The synthetic reconstruction results show that the proposed algorithm has significant advantages compared with the classical algorithms, and the reconstruction by using full-wave data generated by FEKO further verifies the validity of the proposed algorithm. Finally, the proposed algorithm performs as expected over real data acquired by our laboratory prototype.

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

The Usability of Face Coverings Used to Prevent the Spread of COVID-19.

OBJECTIVE: To describe the perceived usability and usability problems associated with face coverings used to prevent the spread of COVID-19. BACKGROUND: Since public health experts have now identified the appropriate use of facemasks as one of the critical elements in an effective COVID mitigation strategy, understanding how people use and care for them has become important. METHOD: Data were collected via a survey that was shared on social media to which 2148 people responded. Participants were asked to identify the category class of the face covering they most often wear, rate its usability, answer demographic information, and questions about their mask use and hygiene, and identify issues they may suffer in relation to face cover use. RESULTS: Overall, users appear to perceive their face coverings favorably from a usability and satisfaction standpoint, even though almost two-thirds of users indicated that they experienced discomfort and problems with glasses fogging with the most popular mask types. When considering demographic information, users' political party affiliation appears related to how they perceive the usability of their face covering. CONCLUSION: Designers should work to improve the fit and comfort properties of protective masks; evidence suggests the System Usability Scale may be a useful tool in those efforts. APPLICATION: Understanding mask design and behavioral issues related to their use can help in the development of masks and will maximize their acceptance and effectiveness in the field.

Blood Flow Restriction Therapy for Use After Extremity Fracture: A Critically Appraised Topic.

CLINICAL SCENARIO: Blood flow restriction (BFR) therapy has emerged as a viable treatment option to enhance clinical recovery in patients with primarily muscular injuries. However, BFR therapy has been rarely investigated in patients with osseous injuries to include extremity fracture. FOCUSED CLINICAL QUESTION: Does BFR-enhanced therapy improve clinical outcomes in patients during the acute to subacute rehabilitation period after extremity fracture? SUMMARY OF KEY FINDINGS: (1) In cases of 2 high-performing athletes with talus and osteochondral fracture of the knee, BFR was well tolerated and an effective rehabilitation regimen. (2) In 2 randomized controlled trials evaluating BFR use in patients after operative and nonoperative management of distal radius fractures, pain with activity and self-perceived function were improved in BFR-enhanced therapy as compared with a standard rehabilitation regimen. (3) Objective clinical outcomes including radiographic healing, extremity range of motion, and grip strength evaluated by the randomized controlled trials did not differ significantly between the BFR-enhanced and standard rehabilitation groups. CLINICAL BOTTOM LINE: BFR-enhanced therapy may improve pain and self-perceived function of the injured extremity during the acute to subacute rehabilitation period after fracture. However, there is not yet a demonstrated benefit of BFR on hastening objective measures of clinical recovery. Large-scale clinical trials comparing BFR-enhanced rehabilitation with standard rehabilitation regimens are needed to better characterize BFR use in patients with osseous injuries. STRENGTH OF RECOMMENDATION: Two case reports and 2 randomized controlled trials provide level IIB evidence suggesting that BFR may improve pain in the acute rehabilitative stage and improve the patient's perceived function of the injured extremity, without greater improvement in objectively measured clinical parameters as compared with a standard rehabilitation regimen.

Variation by default: cesarean section discharge opioid prescription patterns and outcomes in Military Health System hospitals: a retrospective longitudinal cohort study.

BACKGROUND: To examine factors associated with post-Cesarean section analgesic prescription variation at hospital discharge in patients who are opioid naïve; and examine relationships between pre-Cesarean section patient and care-level factors and discharge morphine equivalent dose (MED) on outcomes (e.g., probability of opioid refill within 30 days) across a large healthcare system. METHODS: The Walter Reed Institutional Review Board provided an exempt determination, waiver of consent, and waiver of HIPAA authorization for research use in the present retrospective longitudinal cohort study. Patient records were included in analyses if: sex assigned in the medical record was "female," age was 18 years of age or older, the Cesarean section occurred between January 2016 to December 2019 in the Military Health System, the listed TRICARE sponsor was an active duty service member, hospitalization began no more than three days prior to the Cesarean section, and the patient was discharged to home < 4 days after the Cesarean section. RESULTS: Across 57 facilities, 32,757 adult patients had a single documented Cesarean section procedure in the study period; 24,538 met inclusion criteria and were used in analyses. Post-Cesarean section discharge MED varied by facility, with a median MED of 225 mg and median 5-day supply. Age, active duty status, hospitalization duration, mental health diagnosis, pain diagnosis, substance use disorder, alcohol use disorder, gestational diabetes, discharge opioid type (combined vs. opioid-only medication), concurrent tubal ligation procedure, single (vs. multiple) births, and discharge morphine equivalent dose were associated with the probability of an opioid prescription refill in bivariate analyses, and therefore were included as covariates in a generalized additive mixed model (GAMM). Generalized additive mixed model results indicated that non-active duty beneficiaries, those with mental health and pain conditions, those who received an opioid/non-opioid combination medication, those with multiple births, and older patients were more likely to obtain an opioid refill, relative to their counterparts. CONCLUSION: Significant variation in discharge pain medication prescriptions, as well as the lack of association between discharge opioid MED and probability of refill, indicates that efforts are needed to optimize opioid prescribing and reduce unnecessary healthcare variation.

The Latin American Brain Health Institute, a regional initiative to reduce the scale and impact of dementia.

Latin American and Caribbean countries face complex challenges to improve brain health and reduce the impact of dementia. Regional hubs devoted to research, capacity building, implementation science, and education are critically needed. The Latin American Brain Health Institute represent an important step to address many of these needs.

Impaired posterior cingulate cortex-parahippocampus connectivity is associated with episodic memory retrieval problems in amnestic mild cognitive impairment.

Episodic memory retention and retrieval decline are the most common impairments observed in amnestic mild cognitive impairment (aMCI) patients who progress to Alzheimer's disease (AD). Clinical electroencephalography research shows that patients with dementia due to AD exhibit a slowing of neural electrical activity in the parietal cortex. Memory research has further suggested that successful memory performance is associated with changes in a posterior cingulate-parahippocampal cortical network together with increased θ-γ oscillatory coupling, where θ oscillations act as carrier waves for γ oscillations, which contain the actual information. However, the neurophysiological link between the memory research and clinical studies investigating aMCI and AD is lacking. In this study, we look at brain activity in aMCI and how it relates to memory performance. We demonstrate decreased γ power in the posterior cingulate cortex and the left and right parahippocampus in aMCI patients in comparison to control participants. This goes together with reduced θ coherence between the posterior cingulate cortex and parahippocampus associated with altered memory performance aMCI patients in comparison to control participants. In addition, comparing patients with aMCI to control participants reveals an effect for θ-γ coupling for the posterior cingulate cortex, and the left and right parahippocampus. Taken together, our results show that parahippocampus and posterior cingulate cortex interact via θ-γ coupling, which is associated with memory recollection and is altered in aMCI patients, offering a potential candidate mechanism for memory decline in aMCI.

The Irish experience of kidney transplantation among recipients with prior non-renal solid organ transplants: A retrospective study on short- and long-term outcomes.

BACKGROUND: This study aims to evaluate allograft and patient outcomes among recipients of kidney transplants after non-renal solid organ transplants. We also aim to compare our findings with recipients of a repeat kidney transplant. METHODS: We performed an analysis on kidney transplant recipients who underwent kidney transplantation after a non-renal solid organ transplant. Survival data were stratified into 2 groups: Group A (n = 37) consisted of recipients of a kidney transplant after prior non-renal solid organ transplant, and Group B (n = 330) consisted of recipients of a repeat kidney transplant. RESULTS: The 1-,5-, and 10-year graft survival (death-censored) for recipients of a kidney transplant post-non-renal solid organ transplant (Group A) were 97.3%, 91.5%, and 86.9%, compared with 97.9%, 90.2%, and 83.4% for recipients of a repeat kidney transplant (Group B) (p = .32). The 1-, 5-, and 10-year patient survival rates were 97.3%, 82.7%, and 79.1% in Group A compared to 97.9%, 90.2%, and 83.4% in Group B. Unadjusted overall patient survival was significantly lower for Group A (p = .017). CONCLUSION: Kidney transplant recipients who have undergone a previous non-renal solid organ transplant have similar allograft survival outcomes, but higher long-term mortality rates compared to repeat kidney transplant recipients.

Optimizing fluorine labelling for 19F solid-state NMR in oriented biological systems.

When planning a fluorine labeling strategy for 19F solid state NMR (ssNMR) studies of the structure and/or mobility of fluorine labeled compounds in situ in an oriented biological system, it is important to characterize the NMR properties of the label. This manuscript focuses on the characterization of a selection of aromatic fluorine compounds in dimyristoylphosphatidylcholine bilayers using 19F ssNMR from the standpoint of determining the optimum arrangement of fluorine nuclei on a pendant aromatic ring before incorporation into more complex biological systems.

Substrate integrated Bragg waveguide: an octave-bandwidth single-mode hybrid transmission line for millimeter-wave applications.

We demonstrate an air-core single-mode hollow hybrid waveguide that uses Bragg reflector structures in place of the vertical metal walls of the standard rectangular waveguide or via holes of the so-called substrate integrated waveguide. The high-order modes in the waveguide are substantially suppressed by a modal-filtering effect, making the waveguide operate in the fundamental mode over more than one octave. Numerical simulations show that the propagation loss of the proposed waveguide can be lower than that of classic hollow metallic rectangular waveguides at terahertz frequencies, benefiting from a significant reduction in Ohmic loss. To facilitate fabrication and characterization, a proof-of-concept 20 to 45 GHz waveguide is demonstrated, which verifies the properties and advantages of the proposed waveguide. A zero group-velocity dispersion point is observed at near the middle of the operating band, which is ideal for reducing signal distortion. This work offers a step towards a hybrid transmission-line medium that can be used in a variety of functional components for multilayer integration and broadband applications.

Subclinical infection of captive Asian elephants (Elephas maximus) in Thailand with elephant endotheliotropic herpesvirus.

Elephant endotheliotropic herpesvirus (EEHV) infection is a conservation threat to the endangered Asian elephant (Elephas maximus), causing fatal hemorrhagic disease in juvenile elephants throughout the world, including Thailand. This study revealed a subclinical EEHV1 infection rate of 5.5% in healthy captive Asian elephants in Thailand (n = 362). The virus was detected in all age classes above one year old, in both sexes, and across the country - even in facilities with no history of hemorrhagic disease (EEHV HD). Subclinical EEHV infection in Thailand urgently requires proper health management.

A little too technical: The threat of intellectualising technical reasoning.

Osiurak and Reynaud (O&R) claim that research into the origin of cumulative technological culture has been too focused on social cognition and has consequently neglected the importance of uniquely human reasoning capacities. This commentary raises two interrelated theoretical concerns about O&R's notion of technical-reasoning capacities, and suggests how these concerns might be met.

P3b amplitude as a signature of cognitive decline in the older population: An EEG study enhanced by Functional Source Separation.

With the greying population, it is increasingly necessary to establish robust and individualized markers of cognitive decline. This requires the combination of well-established neural mechanisms, and the development of increasingly sensitive methodologies. The P300 event-related potential (ERP) has been one of the most heavily investigated neural markers of attention and cognition, and studies have reliably shown that changes in the amplitude and latency of the P300 ERP index the process of aging. However, it is still not clear whether either the P3a or P3b sub-components additionally index levels of cognitive impairment. Here, we used a traditional visual three-stimulus oddball paradigm to investigate both the P3a and P3b ERP components in sixteen young and thirty-four healthy elderly individuals with varying degrees of cognitive ability. EEG data extraction was enhanced through the use of a novel signal processing method called Functional Source Separation (FSS) that increases signal-to-noise ratio by using a weighted sum of all electrodes rather than relying on a single, or a small sub-set, of EEG channels. Whilst clear differences in both the P3a and P3b ERPs were seen between young and elderly groups, only P3b amplitude differentiated older people with low memory performance relative to IQ from those with consistent memory and IQ. A machine learning analysis showed that P3b amplitude (derived from FSS analysis) could accurately categorise high and low performing elderly individuals (78% accuracy). A comparison of Bayes Factors found that differences in cognitive decline within the elderly group were 87 times more likely to be detected using FSS compared to the best performing single electrode (Cz). In conclusion, we propose that P3b amplitude could be a sensitive marker of early, age-independent, episodic memory dysfunction within a healthy older population. In addition, we advocate for the use of more advanced signal processing methods, such as FSS, for detecting subtle neural changes in clinical populations.

Plasticity of the Right-Lateralized Cognitive Reserve Network in Ageing.

Cognitive reserve (CR) is the phenomenon where older adults with more cognitively stimulating environments show less age-related cognitive decline. The right-lateralized fronto-parietal network has been proposed to significantly contribute to CR and visual attention in ageing. In this study we tested whether plasticity of this network may be harnessed in ageing.We assessed CR and parameters of visual attention capacity in older adults. Transcranial direct current stimulation (tDCS) was employed to increase right fronto-parietal activity during a lateralized whole-report task. At baseline, older adults with greater CR showed a stronger hemifield asymmetry in processing speed towards the left visual-field, indicative of stronger involvement of the right hemisphere in these individuals. Correspondingly, processing speed improved during right prefrontal tDCS. Older adults with lower levels of CR showed tDCS-related improvements in processing speed in the left but not right hemifield: thus tDCS temporarily altered their processing speed asymmetry to resemble that of their high reserve peers.The finding that stronger right hemisphere involvement is related to CR supports Robertson's theory. Furthermore, preserved plasticity within the right prefrontal cortex in older adults suggests this is a viable target area to improve visual processing speed, a hallmark of age-related decline.

History and epidemiology of foot-and-mouth disease in Afghanistan: a retrospective study.

BACKGROUND: Foot and mouth disease (FMD) is endemic in Afghanistan with serotypes O, A and Asia 1 being prevalent. A retrospective study of data collected through passive surveillance of outbreaks of FMD in Afghanistan from 1995 to 2016 was undertaken to determine the temporal and spatial distribution of FMD in the country. RESULTS: A total of 4171 outbreaks were reported between 1995 and 2008 with a strong correlation between the number of outbreaks and the number of provinces (r = 0.85, s = 68.2, p < 0.001); and between the number of outbreaks and the number of districts containing infected animals (r = 0.68, s = 147.8, p = 0.008). Of 7558 samples collected from livestock originating from 34 provinces in 2009, 2011 and 2013-2015, 54.1% were test positive (FMDV 3ABC-trapping ELISA) and the prevalence varied significantly between years (χ2 = 263.98, df = 4, P < 0.001). Clinically suspected cases were reported in 2016 with a substantial positive correlation (r = 0.70, P < 0.001) between the number of districts with cases and the number of reported cases. Serotype O was the predominant serotype detected during the study period, although serotypes A and Asia1 were also detected. Cattle were involved in all outbreaks in the study period and infections were detected in all years of the study in Hirat province in the north-west (bordering Iran), Nangarhar province in the east (bordering Pakistan) and Kabul province in the centre of the country. CONCLUSIONS: The current paper was the first analysis of existing data focusing on the spatiotemporal distribution of FMD in Afghanistan. The findings from this study provide valuable direction for further research to understand the epidemiology of FMD and its control in Afghanistan.