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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Diffuse optical spectroscopy (DOS) techniques characterize scattering media by examining their optical response to laser illumination. Time-domain DOS methods involve illuminating the medium with a laser pulse and using a fast photodetector to measure the time-dependent intensity of light that exits the medium after multiple scattering events. While DOS research traditionally focused on characterizing biological tissues, we demonstrate that time-domain diffuse optical measurements can also be used to characterize snow. We introduce a model that predicts the time-dependent reflectance of a dry snowpack as a function of its density, grain size, and black carbon content. We develop an algorithm that retrieves these properties from measurements at two wavelengths. To validate our approach, we assembled a two-wavelength lidar system to measure the time-dependent reflectance of snow samples with varying properties. Rather than measuring direct surface returns, our system captures photons that enter and exit the snow at different points, separated by a small distance (4–10 cm). We observe clear, linear correlations between our retrievals of density and black carbon concentration, and ground truth. For black carbon concentration the correlation is nearly one-to-one. We also find that our method is capable of distinguishing between small and large grain sizes.
Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.
Background: Healthcare-associated central line associated bloodstream infection (HA-CLABSI) surveillance is important for monitoring healthcare-associated infections (HAIs) and evaluating effectiveness of infection prevention (IP) measures. However, implementing it is a laborious and time-consuming approach. Exclusive focus on central lines neglects HAI risk due to peripheral vascular catheters. This study aimed to assess whether HA-CLABSI incidence could be inferred from HA-bloodstream infection (BSI) trends and explore shift to HA-BSI surveillance. Methods: The study was performed in a Singaporean tertiary care hospital. Electronic medical records review was performed to determine whether positive blood cultures met Centers for Disease Control/National Health Safety Network (CDC/NHSN) definitions for HA-CLABSI and HA-BSI. Incident episodes of HA-BSI were included (excluding positive cultures repeated within 14 days). Incident organisms were explored to identify common causative pathogens (excluding same organisms isolated from cultures repeated within 14 days). CLABSI and BSI occurring ≥72hrs after admission were considered healthcare-associated. Patients under oncology or hematology service were considered immunocompromised. Incidence rates (IR) per 10,000 patient-days, patient characteristics and causative pathogens were compared between both indicators. Results: From January 2022 to October 2023, mean IR for HA-CLABSI was 0.63 (n=68) and for HA-BSI was 10.06 (n=1094). Median age of patients with HA-CLABSI was 66 years and HA-BSI was 68 years. HA-CLABSI and HA-BSI were more common in males (60.86% & 58.68%). Median duration between admission to HA-CLABSI was 20 days and to HA-BSI was 12 days. Median duration between central line insertion to HA-CLABSI was 16 days. Of 1094, 631 (57.7%) patients had vascular catheter(s) (i.e., IV cannula, port-a-cath, peripherally-inserted central catheter or central line) inserted at time of HA-BSI diagnosis, of whom 46 (7.3%) patients had CLABSI ±2days from positive blood culture. There was no significant correlation between monthly aggregate data from these indicators (Spearman’s correlation coefficient= 0.36, p-value=0.1). Predominant organisms causing HA-CLABSI and HA-BSI were gram negative bacteria (GNB, 40% & 57.21%), gram positive bacteria (24.71% & 22.23%), and fungi. Common GNB in CLABSI patients were Pseudomonas spp. and Stenotrophomonas maltophilia (8.24%), followed by Serratia marcescens and Klebsiella pneumoniae (5.88%). The frequent GNB in HA-BSI patients were Escherichia coli (15.4%), Klebsiella pneumonia (12.68%), and Pseudomonas spp. (6.69%). Common multi-drug resistant organisms were vancomycin-resistant Enterococcus faecium (10.59% & 3.69%) and methicillin-resistant Staphylococcus aureus (10.59% & 3.07%). Conclusion: HA-BSI did not correlate with HA-CLABSI. HA-BSI reflects heterogenous population outcomes. For utilization as surveillance indicator, further assessment on exclusion criteria is required to improve specificity.
Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.
Methods:
CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.
Results:
Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.
Conclusions:
To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.
Internalizing and externalizing problems that emerge during adolescence differentially increase boys’ and girls’ risk for developing psychiatric disorders. It is not clear, however, whether there are sex differences in the intrinsic functional architecture of the brain that underlie changes in the severity of internalizing and externalizing problems in adolescents. Using resting-state fMRI data and self-reports of behavioral problems obtained from 128 adolescents (73 females; 9–14 years old) at two timepoints, we conducted multivoxel pattern analysis to identify resting-state functional connectivity markers at baseline that predict changes in the severity of internalizing and externalizing problems in boys and girls 2 years later. We found sex-differentiated involvement of the default mode network in changes in internalizing and externalizing problems. Whereas changes in internalizing problems were associated with the dorsal medial subsystem in boys and with the medial temporal subsystem in girls, changes in externalizing problems were predicted by hyperconnectivity between core nodes of the DMN and frontoparietal network in boys and hypoconnectivity between the DMN and affective networks in girls. Our results suggest that different neural mechanisms predict changes in internalizing and externalizing problems in adolescent boys and girls and offer insights concerning mechanisms that underlie sex differences in the expression of psychopathology in adolescence.
Thirty years after the discovery of an Early Neolithic timber hall at Balbridie in Scotland was reported in Antiquity, new analysis of the site's archaeobotanical assemblage, featuring 20 000 cereal grains preserved when the building burnt down in the early fourth millennium BC, provides new insights into early farming practices. The results of stable isotope analyses of cereals from Balbridie, alongside archaeobotanical and stable isotope results from three other sites, indicate that while cereals were successfully cultivated in well-established plots without manuring at Balbridie, a variety of manuring strategies was implemented at the other sites. These differences reinforce the picture of variability in cultivation practices across Neolithic North-west Europe.
The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.
Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries.
Methods
Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001–2019). A self-controlled case series design was applied to control for time-invariant confounders.
Results
A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71–5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88–1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09–1.66), p = 0.006].
Conclusions
This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.
There are many structural problems facing the UK at present, from a weakened National Health Service to deeply ingrained inequality. These challenges extend through society to clinical practice and have an impact on current mental health research, which was in a perilous state even before the coronavirus pandemic hit. In this editorial, a group of psychiatric researchers who currently sit on the Academic Faculty of the Royal College of Psychiatrists and represent the breadth of research in mental health from across the UK discuss the challenges faced in academic mental health research. They reflect on the need for additional investment in the specialty and ask whether this is a turning point for the future of mental health research.
1. To explain the reasons for the trend towards R&D decentralization and to describe the difference between ‘home-base-exploiting’ and ‘home-base-augmenting’ innovation sites inside the MNE.
2. To highlight the key stages in the development of foreign R&D units.
3. To explain the role of subsidiary initiatives in the innovation sphere and the functioning of the ‘corporate immune system’, geared towards destroying such initiatives.
4. To foster understanding on how clusters of innovation (COIs) contribute to MNEs’ new upstream FSA development, and function as cross-border ecosystems.
5. To examine the potential conflicts between host country research sites and the corporate office.
1. To describe the four characteristics of core competencies, which are the higher-order firm-specific advantages (FSAs) of the firm.
2. To explain the importance of the corporation’s ‘strategic architecture’ in the context of core competencies.
3. To develop an understanding of MNEs’ business model diversification, whereby the FSAs deployed in each business model, though at least different in part, should also mutually reinforce one another to drive growth and profitability.
4. To identify the bounded rationality and bounded reliability problems associated with MNEs outsourcing their R&D, if they want to maintain or build core competencies in innovation.
5. Based on the conceptual framework in Chapter 1, to analyze the managerial implications of an ill-conceived, sole focus on core competencies.
1. To describe the challenges associated with centralizing strategic decision making and control in MNEs, and to highlight the possible ineffectiveness thereof.
2. To develop a framework for classifying MNE subsidiaries as a function of the location advantages they can access and the unique bundles of FSAs they command inside the firm, but with due consideration to the value chain activities involved.
3. To foster reflection on the ‘procedural justice’ concept and to highlight the impact thereof on decision making and organizational effectiveness.
4. To explain MNEs’ strategic agility in terms of balancing the tensions between head office priorities and local priorities in high distance markets.
5. To highlight the managerial implications of assigning differentiated roles to MNE subsidiaries.