A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Treatment of dissociative identity disorder: leveraging neurobiology to optimize success.

INTRODUCTION: Dissociative identity disorder (DID) is a treatable mental health condition that is associated with a range of psychobiological manifestations. However, historical controversy, modern day misunderstanding, and lack of professional education have prevented accurate treatment information from reaching most clinicians and patients. These obstacles also have slowed empirical efforts to improve treatment outcomes for people with DID. Emerging neurobiological findings in DID provide essential information that can be used to improve treatment outcomes. AREAS COVERED: In this narrative review, the authors discuss symptom characteristics of DID, including dissociative self-states. Current treatment approaches are described, focusing on empirically supported psychotherapeutic interventions for DID and pharmacological agents targeting dissociative symptoms in other conditions. Neurobiological correlates of DID are reviewed, including recent research aimed at identifying a neural signature of DID. EXPERT OPINION: Now is the time to move beyond historical controversy and focus on improving DID treatment availability and efficacy. Neurobiological findings could optimize treatment by reducing shame, aiding assessment, providing novel interventional brain targets and guiding novel pharmacologic and psychotherapeutic interventions. The inclusion of those with lived experience in the design, planning and interpretation of research investigations is another powerful way to improve health outcomes for those with DID.

Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4.

Oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4) have emerged as potentially druggable targets in antiviral and precision cancer drug development. Multiple structurally diverse small molecules function through targeting the OSBP/ORP family of proteins, including the antiviral steroidal compounds OSW-1 and T-00127-HEV2. Here, the structure-activity relationships of oxysterols and related compound binding to human OSBP and ORP4 are characterized. Oxysterols with hydroxylation at various side chain positions (i.e., C-20, C-24, C-25, and C-27)─but not C-22─confer high affinity interactions with OSBP and ORP4. A library of 20(S)-hydroxycholesterol analogues with varying sterol side chains reveal that side chain length modifications are not well tolerated for OSBP and ORP4 interactions. This side chain requirement is contradicted by the high affinity binding of T-00127-HEV2, a steroidal compound lacking the side chain. The binding results, in combination with docking studies using homology models of OSBP and ORP4, suggest multiple modes of steroidal ligand binding to OSBP and ORP4.

Gender-Affirming Surgery in Adolescents and Young Adults: A Review of Ethical and Surgical Considerations.

BACKGROUND: The number of transgender adolescents seeking gender-affirming surgery (GAS) in increasing. Surgical care of the adolescent transgender patient is associated with several unique technical, legal, and ethical factors. The authors present a review of the current literature on gender-affirming surgery for individuals under the age of legal majority and propose directions for future research. METHODS: A scoping review of recent literature was performed to assess evidence on gender-affirming surgery in individuals under the age of legal majority. Articles were included that examined either ethical or technical factors unique to pediatric GAS. Study characteristics and conclusions were analyzed in conjunction with expert opinion. RESULTS: Twelve articles were identified that met inclusion criteria. Ten of these articles discussed ethical challenges in adolescent GAS, seven discussed legal challenges, and five discussed technical challenges. Ethical discussions focused on the principles of beneficence, nonmaleficence, and autonomy. Legal discussions centered on informed consent and insurance coverage. Technical discussions focused on the effects of puberty blockade on natal tissue. CONCLUSIONS: Surgical care of the adolescent transgender patient involves important ethical, legal, and technical considerations that must be addressed by the clinical team. As the population of individuals seeking GAS after puberty blockade increases, future research is needed describing functional and psychosocial outcomes in these individuals.

Preferences for and barriers to gender affirming surgeries in transgender and non-binary individuals.

Background: The transgender/non-binary community continues to be an underserved population in medicine, and our understanding of their interests, disinterests, and barriers to transition-related healthcare is quite limited, especially among the diverse gender identities within the transgender/non-binary umbrella. Aim: To determine the interests, disinterests and barriers to gender affirming surgeries for transgender men, transgender women and non-binary individuals of any birth-assigned sex. Methods: An anonymous, online survey using REDcap was applied across all 50 states and advertised through social media, healthcare organization websites and flyers. The responses of individuals greater than 18 years of age who identified as transgender or non-binary were analyzed. Results: Compared to the 2015 US Transgender Survey, interest in gender affirming surgeries was higher across all gender identities surveyed and for all procedures, by an average of 38%. Interest overall in gender affirming procedures varied greatly among gender identity groups as well as with age differences. Barriers were found to be a mixture of lack of resources for recovery, financial, and a fear of complications. Discussion: Our results highlight that a desire for these procedures is unique for each individual and should never be assumed for transgender/non-binary patients. In order to better aid this underserved population, the medical community must further work to mitigate the barriers to gender affirming procedures by decreasing cost, investigating ways to increase access to resources for recovery, and improving outcomes for each of the gender affirming surgeries.

Deconstructing dissociation: a triple network model of trauma-related dissociation and its subtypes.

Trauma-related pathological dissociation is characterized by disruptions in one's sense of self, perceptual, and affective experience. Dissociation and its trauma-related antecedents disproportionately impact women. However, despite the gender-related prevalence and high individual and societal costs, dissociation remains widely underappreciated in clinical practice. Moreover, dissociation lacks a synthesized neurobiological model across its subtypes. Leveraging the Triple Network Model of psychopathology, we sought to parse heterogeneity in dissociative experience by examining functional connectivity of three core neurocognitive networks as related to: (1) the dimensional dissociation subtypes of depersonalization/derealization and partially-dissociated intrusions; and, (2) the diagnostic category of dissociative identity disorder (DID). Participants were 91 women with and without: a history of childhood trauma, current posttraumatic stress disorder (PTSD), and varied levels of dissociation. Participants provided clinical data about dissociation, PTSD symptoms, childhood maltreatment history, and completed a resting-state functional magnetic resonance imaging scan. We used a novel statistical approach to assess both overlapping and unique contributions of dissociation subtypes. Covarying for age, childhood maltreatment and PTSD severity, we found dissociation was linked to hyperconnectivity within central executive (CEN), default (DN), and salience networks (SN), and decreased connectivity of CEN and SN with other areas. Moreover, we isolated unique connectivity markers associated with depersonalization/derealization in CEN and DN, to partially-dissociated intrusions in CEN, and to DID in CEN. This suggests dissociation subtypes have robust functional connectivity signatures that may serve as targets for PTSD/DID treatment engagement. Our findings underscore dissociation assessment as crucial in clinical care, in particular, to reduce gender-related health disparities.

Anxiety sensitivity predicts depression severity in individuals with dissociative identity disorder.

BACKGROUND: Anxiety sensitivity involves the fear of anxiety-related symptoms and can exacerbate both major depressive disorder and posttraumatic stress disorder (PTSD) symptoms. However, it is unclear if anxiety sensitivity plays a similar role in dissociative identity disorder (DID) where symptoms of depression and PTSD commonly co-occur. We examined the association between anxiety sensitivity, depression, PTSD and dissociative symptoms in DID, hypothesizing a positive association between all symptoms and anxiety sensitivity. METHOD: Participants were 21 treatment-seeking adult females with histories of childhood trauma, current PTSD, and DID. Participants completed the Anxiety Sensitivity Index (ASI), Beck Depression Inventory-II, Childhood Trauma Questionnaire, Multidimensional Inventory of Dissociation, and PTSD Checklist for DSM-5. The ASI included subscales that assessed anxiety sensitivity in cognitive, physical, and social domains. RESULTS: Participants reported high levels of anxiety sensitivity. A multiple regression analysis demonstrated that the ASI cognitive subscale was the strongest predictor of depressive symptoms. No direct associations were identified between anxiety sensitivity and PTSD or dissociative symptoms. We conducted a mediation analysis to test an indirect relationship between cognitive anxiety sensitivity and dissociative symptoms, and found a significant indirect effect through depressive symptoms. CONCLUSIONS: Our results suggest that cognitive anxiety sensitivity or the fear of cognitive dyscontrol is linked with symptom severity in DID. These findings emphasize the need to assess for and utilize interventions that target anxiety sensitivity, which may in turn alleviate symptoms of depression and dissociation in DID.

Current Practices in the Pathologic Assessment of Breast Tissue in Transmasculine Chest Surgery.

BACKGROUND: No guidelines exist regarding management of breast tissue for transmasculine and gender-nonconforming individuals. This study aims to investigate the experiences and practices regarding perioperative breast cancer risk management among the American Society of Plastic Surgeons members performing chest masculinization surgery. METHODS: An anonymous, online, 19-question survey was sent to 2517 U.S.-based American Society of Plastic Surgeons members in October of 2019. RESULTS: A total of 69 responses were analyzed. High-volume surgeons were more likely from academic centers (OR, 4.88; 95 percent CI, 1.67 to 15.22; p = 0.005). Age older than 40 years [ n = 59 (85.5 percent)] and family history of breast cancer in first-degree relatives [ n = 47 (68.1 percent)] or family with a diagnosis before age 40 [ n = 49 (71.0 percent)] were the most common indications for preoperative imaging. Nineteen of the respondents (27.5 percent) routinely excise all macroscopic breast tissue, with 21 (30.4 percent) routinely leaving breast tissue. Fifty-one respondents (73.9 percent) routinely send specimens for pathologic analysis. There was no significant correlation between surgical volume or type of practice and odds of sending specimens for pathologic analysis. High patient costs and patient reluctance [ n = 27 (39.1 percent) and n = 24 (35.3 percent), respectively] were the most often cited barriers for sending specimens for pathologic analysis. Six respondents (8.7 percent) have found malignant or premalignant lesions in masculinizing breast specimens. CONCLUSIONS: Large variation was found among surgeons' perioperative management of chest masculinizing surgery patients regarding preoperative cancer screening, pathologic assessment of resected tissue, and postoperative cancer surveillance. Standardization of care and further studies are needed to document risk, incidence, and prevalence of breast cancer in the transmasculine population before and after surgery.

Unravelling psychiatric heterogeneity and predicting suicide attempts in women with trauma-related dissociation using artificial intelligence.

Background: Suicide is a leading cause of death, and rates of attempted suicide have increased during the COVID-19 pandemic. The under-diagnosed psychiatric phenotype of dissociation is associated with elevated suicidal self-injury; however, it has largely been left out of attempts to predict and prevent suicide.Objective: We designed an artificial intelligence approach to identify dissociative patients and predict prior suicide attempts in an unbiased, data-driven manner.Method: Participants were 30 controls and 93 treatment-seeking female patients with posttraumatic stress disorder (PTSD) and various levels of dissociation, including some with the PTSD dissociative subtype and some with dissociative identity disorder (DID).Results: Unsupervised learning models identified patients along a spectrum of dissociation. Moreover, supervised learning models accurately predicted prior suicide attempts with an F1 score up to 0.83. DID had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in PTSD and DID.Conclusions: These findings expand our understanding of the dissociative phenotype and underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury.

Dissociation, feelings of detachment and disruption in one's sense of self and surroundings, is associated with an elevated risk of suicidal self-injury; however, it has largely been left out of attempts to predict and prevent suicide.Using machine learning techniques, we found dissociative identity disorder had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in posttraumatic stress disorder and dissociative identity disorder.These findings underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury.

Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction.

BACKGROUND: Nosocomial outbreaks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. An outbreak investigation was undertaken using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission. METHODS: A nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic was investigated, involving patients and HCWs, with high coverage of pathogen whole-genome sequences (WGS). The time-varying reproduction number from epidemiological data (Rt) was estimated, and maximum likelihood phylogeny was used to assess genetic diversity of the pathogen. Genomic and epidemiological data were combined into a Bayesian framework to model the directionality of transmission, and a case-control study was performed to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients. FINDINGS: The outbreak lasted from 14th March to 12th April 2020, and involved 37 patients (31 with WGS) and 39 employees (31 with WGS), 37 of whom were HCWs. Peak Rt was estimated to be between 2.2 and 3.6. The phylogenetic tree showed very limited genetic diversity, with 60 of 62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, the analyses suggest that HCWs (one of whom was the index case) played an essential role in cross-transmission, with a significantly greater fraction of infections (P<2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCW cases (46.7%). The excess of transmission from HCWs was higher when considering infection of patients [79.0%; 95% confidence interval (CI) 78.5-79.5%] and frail patients (Clinical Frailty Scale score >5; 82.3%; 95% CI 81.8-83.4%). Furthermore, frail patients were found to be at greater risk for nosocomial COVID-19 than other patients (adjusted odds ratio 6.94, 95% CI 2.13-22.57). INTERPRETATION: This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, this study shows that despite such uncertainty, significant transmission patterns can be observed.

DARK Classics in Chemical Neuroscience: Loperamide.

Loperamide, a popular and inexpensive over-the-counter antidiarrheal medicine, is a potent µ-opioid receptor agonist approved by the U.S. Food and Drug Administration (FDA). It has been on the market since 1976 and is relatively safe with no central nervous system-related side effects when used for a short period of time at the recommended therapeutic dose (2-8 mg/day). In recent years, loperamide has become notoriously known as the "poor man's methadone" for people with substance dependence due to the increase in loperamide overdoses from self-administered medication to treat opioid withdrawal symptoms. As a result, in 2018, the FDA decided to limit the available packaged dose of loperamide to stop prominent abuse. This review provides the synthesis and chemical properties of loperamide as well as the pharmacology and adverse effects of its use and the social effects of such abuse.

Carbohydrate Drink Use During 30 Minutes of Variable-Intensity Exercise Has No Effect on Exercise Performance in Premenarchal Girls.

PURPOSE: This study examined the physiological, perceptual, and performance effects of a 6% carbohydrate (CHO) drink during variable-intensity exercise (VIE) and a postexercise test in premenarchal girls. METHODS: A total of 10 girls (10.4 [0.7] y) participated in the study. VO2peak was assessed, and the girls were familiarized with VIE and performance during the first visit. The trial order (CHO and placebo) was randomly assigned for subsequent visits. The drinks were given before VIE bouts and 1-minute performance (9 mL/kg total). Two 15-minute bouts of VIE were completed (10 repeated sequences of 20%, 55%, and 95% power at VO2peak and maximal sprints) before a 1-minute performance sprint. RESULTS: The mean power, peak power, heart rate (HR), %HRpeak, and rating of perceived exertion during VIE did not differ between trials. However, the peak power decreased, and the rating of perceived exertion increased from the first to the second bout. During the 1-minute performance, there were no differences between the trial (CHO vs placebo) for HR (190 [9] vs 189 [9] bpm), %HRpeak (97.0% [3.2%] vs 96.6% [3.0%]), rating of perceived exertion (7.8 [2.3] vs 8.1 [1.9]), peak power (238 [70] vs 235 [60] W), fatigue index (54.7% [10.0%] vs 55.9% [12.8%]), or total work (9.4 [2.6] vs 9.4 [2.1] kJ). CONCLUSION: CHO supplementation did not alter physiological, perceptual, or performance responses during 30 minutes of VIE or postexercise sprint performance in premenarchal girls.

The in-ear region as a novel anatomical site for ECG signal detection: validation study on healthy volunteers.

PURPOSE: Early detection of cardiac arrhythmias is a major opportunity for mobile health, as wearable devices nowadays available can detect single-lead electrocardiogram (ECG). The study aims to validate the in-ear region as a new anatomical site for ECG signal detection and looks towards designing innovative ECG wearable devices. METHODS: We performed ECG using KardiaMobile device (AliveCor®) on 35 healthy volunteers. First, ECG was detected by standard modality using both hands. Then, ECG was detected using the left in-ear region instead of the right hand. All the recorded ECGs were analyzed by the device and by two cardiologists in blind testing. RESULTS: We successfully collected 70 ECGs performed on 35 volunteers (male 54%, age 39.1 ± 10.7 years; BMI 22.9 ± 2.89 kg/m2) with no differences observed by KardiaMobile in ECG reports detected in the two different modalities. All the ECGs were reported as normal by the device and the two cardiologists. Moreover, linear regression analysis showed good correlation between the amplitude (mV) of P (r = 0.76; r2 = 0.57; p < 0.0001) and QRS waves (r = 0.81; r2 = 0.65; p < 0.0001), the intervals (ms) of PR (r = 0.91; r2 = 0.83; p < 0.0001; LOA - 0.60-0.41; CC = 0.91), QRS (r = 0.78; r2 = 0.61; p < 0.0001; LOA - 0.49-0.43; CC = 0.78), QT (r = 0.85; r2 = 0.71; p < 0.0001; LOA - 1.31-1.20; CC = 0.85), and heart rate (r = 0.94; r2 = 0.89; p < 0.0001; LOA - 7.82-7.76; CC = 0.94) detected in two different modalities. CONCLUSION: The in-ear region is a reliable novel anatomical site for ECG signal detection in normal healthy subjects. Further studies are needed to validate this new ECG detection modality also in case of cardiac arrhythmias and to support the development of new wearable devices.

Microbiota composition modulates inflammation and neointimal hyperplasia after arterial angioplasty.

BACKGROUND: Neointimal hyperplasia is a major contributor to restenosis after arterial interventions, but the genetic and environmental mechanisms underlying the variable propensity for neointimal hyperplasia between individuals, including the role of commensal microbiota, are not well understood. We sought to characterize how shifting the microbiome using cage sharing and bedding mixing between rats with differing restenosis phenotypes after carotid artery balloon angioplasty could alter arterial remodeling. METHODS: We co-housed and mixed bedding between genetically distinct rats (Lewis [LE] and Sprague-Dawley [SD]) that harbor different commensal microbes and that are known to have different neointimal hyperplasia responses to carotid artery balloon angioplasty. Sequencing of the 16S ribosomal RNA gene was used to monitor changes in the gut microbiome. RESULTS: There were significant differences in neointimal hyperplasia between non-co-housed LE and SD rats 14 days after carotid artery angioplasty (mean intima + media [I + M] area, 0.117 ± 0.014 mm2 LE vs 0.275 ± 0.021 mm2 SD; P < .001) that were diminished by co-housing. Co-housing also altered local adventitial Ki67 immunoreactivity, local accumulation of leukocytes and macrophages (total and M2), and interleukin 17A concentration 3 days after surgery in each strain. Non-co-housed SD and LE rats had microbiomes distinguished by both weighted (P = .012) and unweighted (P < .001) UniFrac beta diversity distances, although without significant differences in alpha diversity. The difference in unweighted beta diversity between the fecal microbiota of SD and LE rats was significantly reduced by co-housing. Operational taxonomic units that significantly correlated with average I + M area include Parabacteroides distasonis, Desulfovibrio, Methanosphaera, Peptococcus, and Prevotella. Finally, serum concentrations of microbe-derived metabolites hydroxyanthranilic acid and kynurenine/tryptophan ratio were significantly associated with I + M area in both rat strains independent of co-housing. CONCLUSIONS: We describe a novel mechanism for how microbiome manipulations affect arterial remodeling and the inflammatory response after arterial injury. A greater understanding of the host inflammatory-microbe axis could uncover novel therapeutic targets for the prevention and treatment of restenosis.

Higher integration scores are associated with facial emotion perception differences in dissociative identity disorder.

BACKGROUND: Recovery from dissociative identity disorder (DID) is associated with the process of integration, which includes an increasing sense of self-cohesion and ownership over one's own emotions. Emotion perception is a construction based on interplay between stored knowledge (past experience), and incoming sensory inputs, suggesting changes in emotion perception might occur at different levels of integration - but this remains unexplored. Therefore, we examined the association between integration, psychiatric symptoms, and facial emotion perception. We hypothesized higher integration would be associated with fewer psychiatric symptoms, and differences in the perception of emotions. METHODS: Participants were 82 respondents to a cross-sectional web-based study. All participants met self-report cutoff scores for posttraumatic stress disorder (PTSD) and DID using the PTSD Checklist for DSM-5 and Multiscale Dissociation Inventory, respectively. Participants completed a psychometrically-matched test of facial emotion perception for anger, fear, and happiness called the Belmont Emotion Sensitivity Test. Participants also completed the Beck Depression Inventory II, Childhood Trauma Questionnaire, and Integration Measure, a validated measure of self-cohesion. RESULTS: Higher integration scores were associated with lower depression, PTSD, and autobiographical memory disturbance scores. Repeated-measures ANCOVA confirmed integration significantly interacted with emotion category on the facial emotion perception task. Specifically, higher integration scores were associated with greater accuracy to fearful and angry faces. CONCLUSIONS: While acknowledging the limitations of a cross-sectional design, our results suggest that the process of integration is associated with fewer psychiatric symptoms, and more accurate facial emotion perception. This supports treatment guidelines regarding integration as a therapeutic goal for DID.

Improved inference of time-varying reproduction numbers during infectious disease outbreaks.

Accurate estimation of the parameters characterising infectious disease transmission is vital for optimising control interventions during epidemics. A valuable metric for assessing the current threat posed by an outbreak is the time-dependent reproduction number, i.e. the expected number of secondary cases caused by each infected individual. This quantity can be estimated using data on the numbers of observed new cases at successive times during an epidemic and the distribution of the serial interval (the time between symptomatic cases in a transmission chain). Some methods for estimating the reproduction number rely on pre-existing estimates of the serial interval distribution and assume that the entire outbreak is driven by local transmission. Here we show that accurate inference of current transmissibility, and the uncertainty associated with this estimate, requires: (i) up-to-date observations of the serial interval to be included, and; (ii) cases arising from local transmission to be distinguished from those imported from elsewhere. We demonstrate how pathogen transmissibility can be inferred appropriately using datasets from outbreaks of H1N1 influenza, Ebola virus disease and Middle-East Respiratory Syndrome. We present a tool for estimating the reproduction number in real-time during infectious disease outbreaks accurately, which is available as an R software package (EpiEstim 2.2). It is also accessible as an interactive, user-friendly online interface (EpiEstim App), permitting its use by non-specialists. Our tool is easy to apply for assessing the transmission potential, and hence informing control, during future outbreaks of a wide range of invading pathogens.