Initial Challenges of Caregiving During COVID-19: Caregiver Burden, Mental Health, and the Parent-Child Relationship.

Research confirms that the mental health burdens following community-wide disasters are extensive, with pervasive impacts noted in individuals and families. It is clear that child disaster outcomes are worst among children of highly distressed caregivers, or those caregivers who experience their own negative mental health outcomes from the disaster. The current study used path analysis to examine concurrent patterns of parents' (n = 420) experience from a national sample during the early months of the U.S. COVID-19 pandemic. The results of a multi-group path analysis, organized by parent gender, indicate good fit to the data [X2(10) = 159.04, p < .01]. Results indicate significant linkages between parents' caregiver burden, mental health, and perceptions of children's stress; these in turn are significantly linked to child-parent closeness and conflict, indicating possible spillover effects for depressed parents and compensatory effects for anxious parents. The impact of millions of families sheltering in place during the COVID-19 pandemic for an undefined period of time may lead to unprecedented impacts on individuals' mental health with unknown impacts on child-parent relationships. These impacts may be heightened for families whose caregivers experience increased mental health symptoms, as was the case for fathers in the current sample.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Daily Drinking Is Associated with Increased Mortality.

BACKGROUND: There is evidence that low-level alcohol use, drinking 1 to 2 drinks on occasion, is protective for cardiovascular disease, but increases the risk of cancer. Synthesizing the overall impact of low-level alcohol use on health is therefore complex. The objective of this paper was to examine the association between frequency of low-level drinking and mortality. METHODS: Two data sets with self-reported alcohol use and mortality follow-up were analyzed: 340,668 individuals from the National Health Interview Survey (NHIS) and 93,653 individuals from the Veterans Health Administration (VA) outpatient medical records. Survival analyses were conducted to evaluate the association between low-level drinking frequency and mortality. RESULTS: The minimum risk drinking frequency among those who drink 1 to 2 drinks per occasion was found to be 3.2 times weekly in the NHIS data, based on a continuous measure of drinking frequency, and 2 to 3 times weekly in the VA data. Relative to these individuals with minimum risk, individuals who drink 7 times weekly had an adjusted hazard ratio (HR) of all-cause mortality of 1.23 (p < 0.0001) in the NHIS data, and individuals who drink 4 to 7 times weekly in the VA data also had an adjusted HR of 1.23 (p = 0.01). Secondary analyses in the NHIS data showed that the minimum risk was drinking 4 times weekly for cardiovascular mortality, and drinking monthly or less for cancer mortality. The associations were consistent in stratified analyses of men, women, and never smokers. CONCLUSIONS: The minimum risk of low-level drinking frequency for all-cause mortality appears to be approximately 3 occasions weekly. The robustness of this finding is highlighted in 2 distinctly different data sets: a large epidemiological data set and a data set of veterans sampled from an outpatient clinic. Daily drinking, even at low levels, is detrimental to one's health.

A comparison study of haemolysis production in three contemporary centrifugal pumps.

One challenge in providing extracorporeal circulation is to supply optimal flow while minimising adverse effects, such as haemolysis. To determine if the recent generation constrained vortex pumps with their inherent design improvements would lead to reduced red cell trauma, we undertook a study comparing three devices. Utilizing a simulated short-term ventricular assist circuit primed with whole human blood, we examined changes in plasma free haemoglobin values over a six-day period. The three pumps investigated were the Maquet Rotaflow, the Levitronix PediVAS and the Medos Deltastream DP3.This study demonstrated that all three pumps produced low levels of haemolysis and are suitable for use in a clinical environment. The Levitronix PediVAS was significantly less haemolytic than either the Rotaflow (p<0.05) or the DP3 (p<0.05). There was no significant difference in plasma free haemoglobin between the Rotaflow and the DP3 (p=0.71).

Cardiovascular events among recipients of hematopoietic stem cell transplantation-A systematic review and meta-analysis.

Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of cardiovascular events (CVEs) in this population is not well described. This systematic review summarizes the evidence on the incidence of CVEs in HSCT recipients. Medline and Embase were searched from inception to December 2020. Inclusion criteria were cohort studies and phase 3 randomized controlled trials that reported CVEs among adults who underwent HSCT for hematological malignancies. After reviewing 8386 citations, 57 studies were included. The incidence of CVEs at 100 days was 0.19 (95% CI: 0.17-0.21) per 100 person-days after autologous HSCT and 0.06 (95% CI: 0.05-0.07) per 100 person-days after allogeneic HSCT. This higher incidence after autologous HSCT was driven by reports of arrhythmia from one population-based study in patients with multiple myeloma. The incidence of long-term CVEs was 3.98 (95% CI; 3.44-4.63) per 1000 person-years in survivors of autologous HSCT and 3.06 (95% CI; 2.69-3.48) per 1000 person-years in survivors of allogeneic HSCT. CVEs remain an important but under-reported cause of morbidity and mortality in recipients of HSCT. Future studies are required to better understand the incidence and risk factors for CVEs in HSCT recipients.

Outcome of aortoiliac, femoropopliteal and infrapopliteal endovascular interventions in lesions categorised by TASC classification.

AIM: To analyse lower limb angioplasty results using the defined anatomical classification of the Trans-Atlantic Inter-Society Consensus (TASC) in a training environment and to compare the results with published data. MATERIALS AND METHODS: Retrospective, consecutive data were collected for a period of 1 year for all patients undergoing lower limb endovascular interventions. The radiology information system and notes were used to obtain clinical data, and angiograms were reviewed in all cases. All cases were performed or supervised by five vascular interventional consultants assisted by fellows or registrars. Patient demographics, the indication for treatment, the TASC classification of the treated lesion, calcification, use of stent, technical success (residual stenosis <20% on completion angiography), and complications were assessed. RESULTS: Two hundred and sixty-two lesions were treated. Of the aortoiliac lesions (83), the overall primary technical success rate was 91.6% (TASC A and B: 96.7%, TASC C and D: 77.3%). Sixty-one lesions were stented and no complications recorded. Of the femoropopliteal lesions (n = 123), the overall primary technical success rate was 91.9% (TASC A and B: 98.7%, TASC C and D: 80.9%). There were four major and five minor complications in this group (five groin haematomas, two vessel ruptures, one retroperitoneal haematoma, and one distal embolization). Five patients were stented. In the infrapopliteal group (n = 56), the overall primary technical success rate was 91.1% (TASC A and B: 96.3%, TASC C and D: 86.2%). There was one complication (small retroperitoneal hematoma) and two stents were used. CONCLUSION: The results of the present study showed good technical success and low complication rates in lower limb endovascular interventions with variable operator expertise. The results are comparable to published data. Use of the TASC classification system is encouraged as it allows an objective assessment of severity and enables standardized comparison.

Thematic Analysis of Parent-Child Conversations About COVID-19: "Playing It Safe".

Caregivers have primary responsibility for teaching their children self-protective behaviors, including those behaviors recommended by the Center for Disease Control (CDC) to prevent the spread of COVID-19. Parents have an important role in scaffolding adherence to the CDC recommendations and in managing stress and regulate their emotions to adaptively cope during uncertain times like those facing communities nationwide. The present study is a qualitative, thematic analysis of parent-reported (n = 210; 64.8% female; average age = 39.33; 14.3% ethnic/racial minority) interactions with children (focal child age: 25.2% birth to 5 years old, 36.7% 6 to 11 years old, 37.6% 12 to 18 years old) about topics associated to COVID-19-related viral transmission suppression guidelines and stress/coping behaviors. Themes included discussions about personal and social hygiene, and parent reported sources of child stress, and child stress management efforts. Findings from our thematic analysis indicate parents are motivated to make scaffolding personal hygiene fun and engaging, signaling a positive, developmentally appropriate native approach to their role as sources of coping socialization. These findings also underscore the importance of providing information to parents in ways that can be translated to children in developmentally appropriate conversations about viral transmission suppression activities and stress management during disasters.

A Kinetic Approach for Assessing the Uptake of Ag from Pristine and Sulfidized Ag Nanomaterials to Plants.

Nanomaterials (NMs) are thermodynamically unstable by nature, and exposure of soil organisms to NMs in the terrestrial environment cannot be assumed constant. Thus, steady-state conditions may not apply to NMs, and bioaccumulation modeling for uptake should follow a dynamic approach. The one-compartment model allows the uptake and elimination of a chemical to be determined, while also permitting changes in exposure and growth to be taken into account. The aim of the present study was to investigate the accumulation of Ag from different Ag NM types (20 nm Ag0 NMs, 50 nm Ag0 NMs, and 25 nm Ag2 S NMs) in the crop plant wheat (Triticum aestivum). Seeds were emerged in contaminated soils (3 or 10 mg Ag/kg dry soil, nominal) and plants grown for up to 42 d postemergence. Plant roots and shoots were collected after 1, 7, 14, 21, and 42 d postemergence; and total Ag was measured. Soil porewater Ag concentrations were also measured at each sampling time. Using the plant growth rates in the different treatments and the changing porewater concentrations as parameters, the one-compartment model was used to estimate the uptake and elimination of Ag from the plant tissues. The best fit of the model to the data included growth rate and porewater concentration decline, while showing elimination of Ag to be close to zero. Uptake was highest for Ag0 NMs, and size did not influence their uptake rates. Accumulation of Ag from Ag2 S NMs was lower, as reflected by the lower porewater concentrations. Environ Toxicol Chem 2021;40:1861-1872. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Improvements to the Faraday cup fast ion loss detector and magnetohydrodynamic induced fast ion loss measurements in Joint European Torus plasmas.

Upgrades to electronic hardware and detector design have been made to the JET thin-foil Faraday cup fast ion loss detector [Darrow et al., Rev. Sci. Instrum. 75, 3566 (2004)] in anticipation of the upcoming deuterium-tritium (DT) campaign. An improved foil stack design has been implemented, which greatly reduces the number of foil-to-foil shorts, and triaxial cabling has mitigated ambient noise pickup. Initial tests of 200 kHz digitizers, as opposed to the original 5 kHz digitizers, have provided enhanced analysis techniques and direct coherence measurements of fast ion losses with magnetohydrodynamic activity. We present recent loss measurements in JET deuterium plasmas correlated with kink modes, fishbone modes, edge-localized modes, and sawteeth. Sources of systematic noise are discussed with emphasis on capacitive plasma pickup. Overall, the system upgrades have established a diagnostic capable of recording alpha particle losses due to a wide variety of resonant fast ion transport mechanisms to be used in future DT-experiments and modeling efforts.

Characterization and on-sky demonstration of an integrated photonic spectrograph for astronomy.

We present results from the first on-sky demonstration of a prototype astronomical integrated photonic spectrograph (IPS) using the Anglo-Australian Telescope near-infrared imaging spectrometer (IRIS2) at Siding Spring Observatory to observe atmospheric molecular OH emission lines. We have succeeded in detecting upwards of 27 lines, and demonstrated the practicality of the IPS device for astronomy. Furthermore, we present a laboratory characterization of the device, which is a modified version of a commercial arrayed-waveguide grating multiplexer. We measure the spectral resolution full-width-half-maximum to be 0.75 +/- 0.05 nm (giving R = lambda/deltalambda = 2100 +/- 150 at 1500 nm). We find the free spectral range to be 57.4 +/- 0.6 nm and the peak total efficiency to be approximately 65%. Finally, we briefly discuss the future steps required to realize an astronomical instrument based on this technology concept.

Ultrasound-derived fetal size nomogram for a sub-Saharan African population: a longitudinal study.

OBJECTIVES: To create a fetal size nomogram for use in sub-Saharan Africa and compare the derived centiles with reference intervals from developed countries. METHODS: Fetal biometric measurements were obtained at entry to antenatal care (11-22 weeks' gestation) and thereafter at 4-week intervals from pregnant women enrolled in a longitudinal ultrasound study in Kinshasa, Democratic Republic of Congo. The study population comprised 144 singleton gestations with ultrasound-derived gestational age within 14 days of the menstrual estimate. A total of 755 monthly ultrasound scans were included with a mean +/- SD of 5 +/- 1 (range, 2-8) scans per woman. Estimated fetal weight (EFW) was calculated at each ultrasound examination using the Hadlock algorithm. A general mixed-effects linear regression model that incorporated random effects for both the intercept and slope was fitted to log-transformed EFW to account for both mean growth and within-fetus variability in growth. Reference centiles (5(th), 10(th), 50(th), 90(th) and 95(th) centiles) were derived from this model. RESULTS: Nomograms derived from developed populations consistently overestimated the 50(th) centile EFW value for Congolese fetuses by roughly 5-12%. Differences observed in the 10(th) and 90(th) centiles were inconsistent between nomograms, but generally followed a pattern of overestimation that decreased with advancing gestational age. CONCLUSIONS: In low-resource settings, endemic malaria and maternal nutritional factors, including low prepregnancy weight and pregnancy weight gain, probably lead to lower fetal weight and utilization of nomograms derived from developed populations is not appropriate. This customized nomogram could provide more applicable reference intervals for diagnosis of intrauterine growth restriction in sub-Saharan African populations.

GDNF is an age-specific survival factor for sensory and autonomic neurons.

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of two populations of CNS neurons: motoneurons and midbrain dopaminergic neurons. To see whether GDNF promotes the survival of PNS neurons, we studied embryonic chicken autonomic and sensory neurons in culture. We show that GDNF promotes the survival of sympathetic, parasympathetic, proprioceptive, enteroceptive, and small and large cutaneous sensory neurons. Whereas sympathetic, parasympathetic, and proprioceptive neurons become less responsive to GDNF with age, enteroceptive and cutaneous sensory neurons become more responsive. GDNF mRNA is expressed in the tissues innervated by these neurons, and developmental changes in its expression in several tissues mirror the changing responses of the innervating neurons to GDNF. These results show that GDNF promotes the survival of multiple PNS and CNS neurons and suggest that GDNF may be important for regulating the survival of various populations of neurons at different stages of their development.

Subject-specific non-linear biomechanical model of needle insertion into brain.

The previous models for predicting the forces acting on a needle during insertion into very soft organs (such as, e.g. brain) relied on oversimplifying assumptions of linear elasticity and specific experimentally derived functions for determining needle-tissue interactions. In this contribution, we propose a more general approach in which the needle forces are determined directly from the equations of continuum mechanics using fully non-linear finite element procedures that account for large deformations (geometric non-linearity) and non-linear stress-strain relationship (material non-linearity) of soft tissues. We applied these procedures to model needle insertion into a swine brain using the constitutive properties determined from the experiments on tissue samples obtained from the same brain (i.e. the subject-specific constitutive properties were used). We focused on the insertion phase preceding puncture of the brain meninges and obtained a very accurate prediction of the needle force. This demonstrates the utility of non-linear finite element procedures in patient-specific modelling of needle insertion into soft organs such as, e.g. brain.

Risk of bladder tumors among benzidine workers and their serum properdin levels.

Serum properdin levels were determined for 21 benzidine operators at 6-month intervals for 2 years after termination of exposure to this carcinogen. Of this group, 7 developed bladder cancers within a 4-month period prior to the initial assay, and all 7 showed properdin levels below the median for the group as a whole. Two of the 3 workers who had had a brief exposure previously to beta-naphthylamine developed benign bladder tumors but had no malignant neoplasms up to 13 years later. The properdin assays of these 3 men remained consistently at or above the median values. No man developed a bladder tumor who was exposed less than 6 years to benzidine, even though 2 of these men showed low properdin levels. Of the 4 whose properdin levels were initially above the median but dropped below in subsequent assays, 3 developed bladder cancers 0.5, 4, and 9 years later. Only 1 man whose properdin level remained high in 1958-59 developed a bladder cancer 7 years later, and his immunologic picture may have been complicated by recovery from a larynx tumor in 1954. Recurrence of bladder tumors among the original 9 cases has occurred only among the 5 whose properdin levels remained below the median. The 1 whose ranking fell most dramatically (from 13 to 19) has had 13 recurrences in 13 years.

Correlation of cocarcinogenic activity among n-alkanes with their physical effects on phospholipid micelles.

N-alkanes from C12 to C28 were tested for their cocarcinogenic or promoting activities to evaluate a correlation of their biologic activity with their effects on transport properties of phospholipid micelles. On this basis, we had predicted that the C18 and C20 homologues would be more active than the better known dodecane. The C12, C16, C18, and C20 n-alkanes, at various dilutions from 6 to 40% by volume in decahydronaphthalene (Decalin), were tested for their relative activity in a cocarcinogenic relationship to benzo[a]pyrene. At a 20% alkane concentration level, the solutions containing octadecane and eicosane induced tumors most rapidly. A 40% dodecane concentration was required to produce this level of cocarcinogenic activity. The activity of octadecane paralleled its physical effects on transport kinetics closely in the 6-40% (by volume) concentration. The C18, C20, and C28 n-alkanes and the C30 olefin squalene at dilutions from 10 to 40% in Decalin (by volume) were tested for their relative promoting activity after a single application of 7,12-dimethylbenz[a]anthracene in benzene. At comparable mole fractions in Decalin, the three n-alkanes had essentially the same promoting activity; squalene, at 20%, showed only borderline activity. Thus the high biologic activity of the C18, C20, and C28 n-alkanes correlated well with their physical effects on the structure of phospholipid micelles (chain-chain interactions of the alkanes with the acyl chains of the lipid). This correlation was interpreted as a strong indication that the liquid crystalline region of the phospholipid assembly (adjacent to the aqueous interface) in the membranes of latent (initiated) cancer cells was the site of action of hydrocarbon cocarcinogens. Application of a modified physical model to pristane, a branched-chain C19 alkane from coal and Colorado shale, indicated higher cocarcinogenic activity than that of n-C18H38. Applied to purified samples of docosane and tetracosane, activity comparable to that of octadecane was indicated.

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as standard, with extension to 240 hour exposures further improving realism.

Prevention of Ca(2+)-induced or thromboxane B2-induced hepatocyte plasma membrane bleb formation by thromboxane receptor antagonists.

Isolated hepatocytes incubated in the presence of either Ca2+ ionophore A23187 or thromboxane B2 develop many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes are incubated in the presence of both Ca2+ ionophore A23187 and any one of three thromboxane receptor antagonists (SK and F 88046, B.M. 13505, B.M. 13177), bleb formation is strongly inhibited. Hepatocytes incubated in the presence of both thromboxane B2 and any one of the three thromboxane receptor antagonists are also well protected from the formation of blebs. Treatment of isolated hepatocytes with Ca2+ ionophore A23187 is known to stimulate the production of thromboxanes. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonate cascade.

Prevention of thromboxane B2-induced hepatocyte plasma membrane bleb formation by certain prostaglandins and a proteinase inhibitor.

Isolated hepatocytes incubated in the presence of thromboxane B2 developed many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes were incubated in the presence of both thromboxane B2 and the non-lysosomal proteinase inhibitor, leupeptin, were also well protected from the formation of blebs. This implies that thromboxane B2 is able to activate non-lysosomal proteinases which appear to attack certain cytoskeletal proteins. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonic acid cascade.

Suppression of milk secretion (exocytosis) by concanavalin a in vitro.

The observation that concanavalin A can inhibit milk secretion was evaluated in an in vitro system employing minced mammary gland or isolated alveoli from lactating rats. Release of milk constituents (casein, lactose and fat globules) into the medium in the presence and absence of concanavalin A was measured during 1 or 2 h incubations. The effect of concanavalin A on glucose uptake and CO2 production of the minced tissue was also studied. Concanavalin A suppressed release of milk components at a concentration as low as 80 micrograms/ml of medium. Respiration of minced mammary tissue in the presence of concanavalin A (100 micrograms/ml of medium) was essentially the same as that of the control. The data are evidence that concanavalin A acts directly on the mammary cell in suppressing milk secretion and that the effect is not due to cytotoxicity.