Social network position is a major predictor of ant behavior, microbiota composition, and brain gene expression.

The physiology and behavior of social organisms correlate with their social environments. However, because social environments are typically confounded by age and physical environments (i.e., spatial location and associated abiotic factors), these correlations are usually difficult to interpret. For example, associations between an individual's social environment and its gene expression patterns may result from both factors being driven by age or behavior. Simultaneous measurement of pertinent variables and quantification of the correlations between these variables can indicate whether relationships are direct (and possibly causal) or indirect. Here, we combine demographic and automated behavioral tracking with a multiomic approach to dissect the correlation structure among the social and physical environment, age, behavior, brain gene expression, and microbiota composition in the carpenter ant Camponotus fellah. Variations in physiology and behavior were most strongly correlated with the social environment. Moreover, seemingly strong correlations between brain gene expression and microbiota composition, physical environment, age, and behavior became weak when controlling for the social environment. Consistent with this, a machine learning analysis revealed that from brain gene expression data, an individual's social environment can be more accurately predicted than any other behavioral metric. These results indicate that social environment is a key regulator of behavior and physiology.

Ant social network structure is highly conserved across species.

The ecological success of social insects makes their colony organization fascinating to scientists studying collective systems. In recent years, the combination of automated behavioural tracking and social network analysis has deepened our understanding of many aspects of colony organization. However, because studies have typically worked with single species, we know little about interspecific variation in network structure. Here, we conduct a comparative network analysis across five ant species from five subfamilies, separated by more than 100 Myr of evolution. We find that social network structure is highly conserved across subfamilies. All species studied form modular networks, with two social communities, a similar distribution of individuals between the two communities, and equivalent mapping of task performance onto the communities. Against this backdrop of organizational similarity, queens of the different species occupied qualitatively distinct network positions. The deep conservation of the two community structure implies that the most fundamental behavioural division of labour in social insects is between workers that stay in the nest to rear brood, and those that leave the nest to forage. This division has parallels across the animal kingdom in systems of biparental care and probably represents the most readily evolvable form of behavioural division of labour.

Are dysfunctional attitudes elevated and linked to mood in bipolar disorder? A systematic review and meta-analysis.

OBJECTIVES: Dysfunctional attitudes (DA) are higher in depression; however, less is understood about their role in bipolar disorder (BD). This paper aimed to explore the presence of DA in BD in comparison to clinical and non-clinical groups. Also explored were the associations between DA and mood states of depression, mania or euthymia in BD. METHODS: A systematic review and meta-analysis were conducted. A total of 47 articles were included in the systematic review of which 23 were included in the meta-analysis. The quality of each study was rated. RESULTS: The meta-analysis showed significantly higher DA in BD than healthy controls (d = .70). However, no difference was observed between BD and unipolar participants (d = -.16). When reviewing mood state within BD, a significant mean difference was found between DA scores for euthymic and depressed participants (d = -.71), with those who were depressed scoring higher. Three studies found that psychological therapies significantly reduce DA in BD (d = -.38). CONCLUSIONS: These findings imply not only that DA are both a characteristic of BD that is not as prevalent in healthy populations but also that a depressed mood state is associated with increased severity. This implies that DA could possibly go 'offline' when mood symptoms are not present. Psychological therapies appear to reduce DA in BD. Implications for future research as well as practice-based implications are expanded on in the discussion.

Is there a 'bipolar iceberg' in UK primary care psychological therapy services?

BACKGROUND: Improving Access to Psychological Therapies (IAPT) is a primary care therapy service commissioned by England's National Health Service (NHS) for people with unipolar depression and anxiety-related disorders. Its scope does not extend to 'severe mental illness', including bipolar disorders (BD), but evidence suggests there is a high BD prevalence in ostensibly unipolar major depressive disorder (uMDD) samples. This study aimed to indicate the prevalence and characteristics of people with BD in a naturalistic cohort of IAPT patients. METHODS: 371 participants were assessed before initiating therapy. Participants were categorised by indicated diagnoses: BD type-I (BD-I) or type-II (BD-II) as defined using a DSM diagnostic interview, bipolar spectrum (BSp, not meeting diagnostic criteria but exceeding BD screening thresholds), lifetime uMDD or other. Information about psychiatric history and co-morbidities was examined, along with symptoms before and after therapy. RESULTS: 368 patients provided sufficient data to enable classification. 10% of participants were grouped as having BD-I, 20% BD-II, 40% BSp, 25% uMDD and 5% other. BD and uMDD participants had similar demographic characteristics, but patients meeting criteria for BD-I/BD-II had more complex psychiatric presentations. All three 'bipolar' groups had particularly high rates of anxiety disorders. IAPT therapy receipt was comparable between groups, as was therapy response (F9704 = 1.113, p = 0.351). CONCLUSIONS: Notwithstanding the possibility that bipolar diathesis was overestimated, findings illustrate a high prevalence of BD in groups of people notionally with uMDD or anxiety. As well as improving the detection of BD, further substantive investigation is required to establish whether individuals affected by BD should be eligible for primary care psychological intervention.

Coherent modeling of longitudinal causal effects on binary outcomes.

Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Toward this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the noncausal nuisance parameters. This leads to a series of difficulties in interpretation, estimation, and computation. These difficulties have hindered the uptake of SNMMs in biomedical practice, where binary outcomes are very common. We solve the variation dependence problem for the binary multiplicative SNMM via a reparameterization of the noncausal nuisance parameters. Our novel nuisance parameters are variation independent of the causal parameters, and hence allow for coherent modeling of heterogeneous effects from longitudinal studies with binary outcomes. Our parameterization also provides a key building block for flexible doubly robust estimation of the causal parameters. Along the way, we prove that an additive SNMM with binary outcomes does not admit a variation independent parameterization, thereby justifying the restriction to multiplicative SNMMs.

Self-compassion as a mediator of the relationship between childhood sexual abuse and psychotic symptoms in clinical and non-clinical groups.

BACKGROUND: Previous research has shown a link between childhood sexual abuse (CSA) and more severe symptoms of psychosis. There is also evidence that self-compassion is a key mechanism linking adverse childhood experiences and mental health problems such as post-traumatic stress disorder and depression, but no research has examined these links in psychosis. METHODS: We analysed existing cross-sectional data, including 55 individuals with psychosis and 166 individuals from the general population. Participants completed standardized measures of CSA, self-compassion, paranoia, positive psychotic symptoms and distress linked to psychosis. RESULTS: The clinical group had higher scores on CSA and all psychosis measures, but we found no differences in self-compassion between the groups. Higher levels of CSA correlated with lower self-compassion and higher paranoia and positive symptoms in both groups. CSA also correlated with distress linked to psychosis in the non-clinical group. Lower self-compassion mediated the association between higher levels of CSA and more severe paranoia in both groups. In the non-clinical group, lower self-compassion also mediated the association between greater CSA and more positive psychotic symptoms and more severe distress. CONCLUSIONS: This is the first study to show that self-compassion mediates the link between CSA and both paranoia and psychotic symptoms in adulthood. Self-compassion may therefore be an important transdiagnostic candidate target in therapy to mitigate the impact of early adversity on paranoia in both clinical and non-clinical groups. Limitations include the small clinical sample and inclusion of a cannabis-using non-clinical sample, though recent cannabis use did not impact self-compassion levels.

Orbital cellulitis and cavernous sinus thrombosis with contralateral sinus disease in a COVID-19 positive adolescent patient.

Patients with COVID-19 have been reported to have elevated coagulation factors, which is a well-documented cause of venous thromboembolism events such as deep vein thrombosis and pulmonary embolism. Other venous thrombotic events, however, such as cavernous sinus thrombosis (CST) have been less commonly observed, specifically in combination with primary orbital cellulitis. Due to its unique anatomic location, the cavernous sinus is susceptible to thrombophlebitis processes including septic thrombosis and thrombosis most commonly from sinusitis. Many studies have shown that in the antibiotic era thromboembolic events of the cavernous sinus are less common due to infection spread from the orbit or facial region. This case report describes a 17-year-old COVID-19 positive male who presented with a left-sided primary orbital cellulitis with CST without radiographic evidence of ipsilateral sinus disease.

No association between adult sex steroids and hand preference in humans.

BACKGROUND: There is ongoing debate about the effects of hormones on the lateralization of the developing brain. In humans, there are conflicting theories of how testosterone during development should affect lateralization. Empirical studies linking prenatal and postnatal testosterone levels to hand preference (a proxy for lateralization) are similarly mixed. Links between hand preference and health may also suggest a mediating role of steroid hormones such as testosterone and estradiol. Studies to date of adult steroid hormones and handedness have been hindered by samples that contain small numbers of non-right-handers. RESULTS: In the largest study of the phenomenon to date, I find that the testosterone (n = 7290) and estradiol (n = 3700) levels of left- and mixed-handed adults are no different to those of right-handers. All Bayesian 95% highest density intervals contained 0. DISCUSSION AND CONCLUSIONS: The results have implications for studies that show elevated risk of hormonal-related mental and physical disorders in left-handed individuals.

Comparison of comprehensive complication index and Clavien-Dindo classification in patients with retroperitoneal sarcoma.

BACKGROUND: Our study aimed to compare the comprehensive complication index (CCI) to the conventional Clavien-Dindo classification (CDC) in patients undergoing surgery for primary retroperitoneal sarcoma (RPS). METHODS: Data were collected for patients who underwent surgery from 2008 to 2019 at a tertiary institution. The length of hospital stay (LOS) was used as a surrogate marker for clinical outcomes, and associations with CDC and CCI were assessed. RESULTS: Data were available for 191 patients, with the highest CDC Grade of I, II, III, and IV in 18.3%, 41.9%, 17.8%, and 4.2%, respectively; the 30-day postoperative mortality (CDC Grade V) was 1.6% (N = 3). Whilst both classification systems were significantly correlated with LOS, this association was significantly stronger for CCI (Spearman's ρ: 0.768 vs. 0.648, p < 0.001). Increasing Charlson Comorbidity Index, tumor size, and organ weighted resection scores were independently associated with longer LOS. However, the association between LOS and both the CDC and CCI remained significant, even after adjusting for these factors (both p < 0.001). CONCLUSION: The CCI is more strongly associated with LOS than the CDC, and represents a useful tool to quantify the total burden of postoperative complications after surgery for RPS.

Financial difficulties in bipolar disorder part 2: psychological correlates and a proposed psychological model.

OBJECTIVES: A number of psychological variables have been shown to be prominent in bipolar disorder. However, no research has looked at the relationship between financial difficulties and psychological factors in bipolar disorder. AIMS: This study aims to look at the relationship between financial difficulties and psychological factors in bipolar disorder. METHOD: Fifty-four participants with diagnosis of bipolar disorder in an adult secondary care NHS mental health service completed the questionnaire pack which included measures examining financial variables including difficulty paying bills and perceived financial wellbeing. Questionnaires measured self-esteem, impulsivity, mindfulness and dysfunctional attitudes. RESULTS: Financial difficulties cross-sectionally were related to a number of psychological variables such as mindfulness and impulsivity. Over time, the strongest effects were for compulsive spending which was increased over time by higher dependency and achievement cognitions, lower mindfulness and lower self-esteem. Poor perceived financial wellness lower self-esteem over time. A psychological model incorporating these and related findings is presented. CONCLUSION: Psychological factors appear to be related to financial difficulties in bipolar disorder. Future research is needed to confirm the model presented here and develop interventions.

Ambient-pressure endstation of the Versatile Soft X-ray (VerSoX) beamline at Diamond Light Source.

The ambient-pressure endstation and branchline of the Versatile Soft X-ray (VerSoX) beamline B07 at Diamond Light Source serves a very diverse user community studying heterogeneous catalysts, pharmaceuticals and biomaterials under realistic conditions, liquids and ices, and novel electronic, photonic and battery materials. The instrument facilitates studies of the near-surface chemical composition, electronic and geometric structure of a variety of samples using X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectroscopy in the photon energy range from 170 eV to 2800 eV. The beamline provides a resolving power hν/Δ(hν) > 5000 at a photon flux > 1010 photons s-1 over most of its energy range. By operating the optical elements in a low-pressure oxygen atmosphere, carbon contamination can be almost completely eliminated, which makes the beamline particularly suitable for carbon K-edge NEXAFS. The endstation can be operated at pressures up to 100 mbar, whereby XPS can be routinely performed up to 30 mbar. A selection of typical data demonstrates the capability of the instrument to analyse details of the surface composition of solid samples under ambient-pressure conditions using XPS and NEXAFS. In addition, it offers a convenient way of analysing the gas phase through X-ray absorption spectroscopy. Short XPS spectra can be measured at a time scale of tens of seconds. The shortest data acquisition times for NEXAFS are around 0.5 s per data point.

Do Locus of Control, Self-esteem, Hope and Shame Mediate the Relationship Between Financial Hardship and Mental Health?

In a longitudinal study of 104 participants, the psychological factors of economic locus of control, self-esteem, hope and shame were explored for their impact on the relationship between financial hardship and mental health. Participants completed measures of financial hardship, the psychological factors and measures of mental health three times at three-monthly intervals. A hierarchical regression analyses indicated that subjective financial hardship, hope and shame significantly predicted mental health outcomes. Mediation analyses demonstrated that hope mediated the relationship between subjective financial hardship and depression, stress and wellbeing; that shame mediated the relationship between subjective financial hardship and anxiety; and that neither shame nor hope mediated the relationship between subjective financial hardship and suicide ideation.

Development and validation of the Readiness for Therapy Questionnaire (RTQ).

BACKGROUND: Motivational factors are generally regarded as an important ingredient for change in therapy. However, there is currently a lack of available instruments that can measure clients' readiness for change in therapy. AIM: The objective of this paper was to create an instrument, the Readiness for Therapy Questionnaire (RTQ), which could measure clients' readiness for change. METHOD: The RTQ was created by researchers following analysis of themes drawn from a review of the literature and interviews with patients at the end of therapy. This included both people who completed therapy and those who dropped out. As part of the standard assessment process, the RTQ was administered to 349 participants (69.6% female and 30.4% male; mean age 37.1 years; 90.5% Caucasian) who were patients at a psychological therapy service for common mental health difficulties. RESULT: An initial 12-item scale was reduced to 6 items. This scale significantly correlated with post-therapy PHQ-9 and GAD-7 scores and changes in these scores across therapy. After controlling for baseline scores and demographic variables, a logistic regression showed that scores on this 6-item measure pre-therapy significantly predicted three outcome variables: completing therapy, being recovered on both PHQ-9 and GAD-7 post-therapy, and having a reliable change in both the PHQ-9 and GAD-7 post-therapy. However, receiver operating characteristic (ROC) curve analysis showed the measure had poor sensitivity and specificity. Symptom severity did not have a significant impact on motivation to change. CONCLUSION: The RTQ is potentially a valid measure with useful clinical applications in treatment of common mental health difficulties.

The Clinical and Financial Impact of a Pharmacist-Driven Penicillin Skin Testing Program on Antimicrobial Stewardship Practices.

Purpose: Pharmacist-led penicillin skin testing (PST) was incorporated into antimicrobial stewardship at a community hospital to increase use of optimal antimicrobial therapy, reduce use of broad-spectrum agents, and reduce antimicrobial therapy-related costs. Methods: A clinical decision support software alert identified qualifying patients with penicillin allergies. Patients receiving a nonoptimal antimicrobial agent were prioritized for PST. Patients were excluded if they reported a history of extreme hypersensitivity to a penicillin agent, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or mucocutaneous eruption with epidermal detachment. Pediatric patients less than 18 years old and pregnant patients were excluded. Data collected for each patient included the medication that precipitated the reaction; reaction type; age when the reaction occurred; current antibiotic therapy; indication for therapy; preferred antimicrobial agent; days of therapy on each agent used; positive, negative, or ambiguous PST result; recent antihistamine use; and any adverse events that occurred. Outcomes of the PST results, pharmacist interventions made after PST, and resulting cost savings to patients were all reported. Results: Among 31 patients tested, 27 were negative for penicillin allergy, 1 was positive for penicillin allergy, and 3 yielded an indeterminate test. Pharmacist recommendation to change therapy based on PST results was accepted in 13 of 15 patients where recommendations were made. Cost savings in antimicrobial therapy alone for patients who received PST was US $74.75 per day. Conclusion: Pharmacist-driven PST provided opportunities to clarify allergies, optimize antimicrobial therapy, and save antimicrobial therapy-related costs to patients.

Computational fluid dynamics modeling, a novel, and effective approach for developing scalable cell therapy manufacturing processes.

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor-intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high-quality iPSC derivatives under controlled conditions. The current scale-up methods used in cell therapy processes are based on empirical, geometry-dependent methods that do not accurately represent the hydrodynamics of 3D bioreactors. These methods require multiple iterations of scale-up studies, resulting in increased development cost and time. Here we show a novel approach using computational fluid dynamics modeling to effectively scale-up cell therapy manufacturing processes in 3D bioreactors. Using a GMP-compatible iPSC line, we translated and scaled-up a small-scale cardiomyocyte differentiation process to a 3-L computer-controlled bioreactor in an efficient manner, showing comparability in both systems.

Predictors of disengagement from cognitive behavioural therapy for psychosis in a National Health Service setting: A retrospective evaluation.

OBJECTIVES: To evaluate whether demographic and clinical variables are related to disengagement rates in cognitive behavioural therapy (CBT) for psychosis in a clinical setting. METHODS: The medical records and symptom severity data (from Health of the Nation Outcome Scales) were analysed retrospectively for 103 referrals for CBT for psychosis in a National Health Service secondary care and Early Intervention in Psychosis team. RESULTS: Overall, 42.7% (n = 44) disengaged from CBT. There was no impact of gender or ethnicity, and no impact of clinical variables such as risk history and comorbid diagnosis. However, risk of disengagement was significantly higher for those who were younger, F = 6.89, partial η2  = .064, p = <.05; those with greater total HoNOS scores, F = 4.22, partial η2  = .04, p < .05; more severe symptoms on the HoNOS items of overactive, aggressive, disruptive, or agitated behaviour, χ2  = 6.13, p < .01; problem drinking or drug taking, χ2  = 7.65, p < .05; depressed mood, χ2  = 7.0, p < .01; and problems with occupation and activities: χ2  = 3.68, p < .05. There was a non-significant trend for shorter waiting times to be associated with greater levels of disengagement. CONCLUSIONS: These results indicate that it may not be psychosis per se that disrupts engagement in CBT, but linked behavioural and emotional factors. A more assertive approach to these factors - overactive, aggressive, disruptive, or agitated behaviour, problem drinking or drug taking, depressed mood, and problems with occupation and activities, particularly in younger people - may be valuable prior to or early on in therapy as a means of increasing engagement in CBT for psychosis. PRACTITIONER POINTS: Risk of disengagement from CBT for psychosis increases with overactive, aggressive, disruptive, or agitated behaviour (54.9% vs. 30.8%), problem drinking and drug taking (61.1% vs. 32.8%), depressed mood (56% vs. 30.2%), and problems with occupation and activities (53.3% vs. 34.5%), with a trend for younger age. An assertive and motivational approach to engagement and a focus on addressing low mood and problematic behaviours, prior to or early in therapy, may be warranted, particularly for younger people. This evaluation is limited by small sample size and being retrospective. These results speak to the question of whether psychosis itself renders people inappropriate for CBT for psychosis, or whether problems arise due to behavioural and emotional factors that might be addressed to increase access to CBT for psychosis.

Long-Term Stability and Differentiation Potential of Cryopreserved cGMP-Compliant Human Induced Pluripotent Stem Cells.

The clinical effectiveness of human induced pluripotent stem cells (iPSCs) is highly dependent on a few key quality characteristics including the generation of high quality cell bank, long-term genomic stability, post-thaw viability, plating efficiency, retention of pluripotency, directed differentiation, purity, potency, and sterility. We have already reported the establishment of iPSC master cell banks (MCBs) and working cell banks (WCBs) under current good manufacturing procedure (cGMP)-compliant conditions. In this study, we assessed the cellular and genomic stability of the iPSC lines generated and cryopreserved five years ago under cGMP-compliant conditions. iPSC lines were thawed, characterized, and directly differentiated into cells from three germ layers including cardiomyocytes (CMs), neural stem cells (NSCs), and definitive endoderm (DE). The cells were also expanded in 2D and 3D spinner flasks to evaluate their long-term expansion potential in matrix-dependent and feeder-free culture environment. All three lines successfully thawed and attached to the L7TM matrix, and formed typical iPSC colonies that expressed pluripotency markers over 15 passages. iPSCs maintained their differentiation potential as demonstrated with spontaneous and directed differentiation to the three germ layers and corresponding expression of specific markers, respectfully. Furthermore, post-thaw cells showed normal karyotype, negative mycoplasma, and sterility testing. These cells maintained both their 2D and 3D proliferation potential after five years of cryopreservation without acquiring karyotype abnormality, loss of pluripotency, and telomerase activity. These results illustrate the long-term stability of cGMP iPSC lines, which is an important step in establishing a reliable, long-term source of starting materials for clinical and commercial manufacturing of iPSC-derived cell therapy products.

The influence of the few: a stable 'oligarchy' controls information flow in house-hunting ants.

Animals that live together in groups often face difficult choices, such as which food resource to exploit, or which direction to flee in response to a predator. When there are costs associated with deadlock or group fragmentation, it is essential that the group achieves a consensus decision. Here, we study consensus formation in emigrating ant colonies faced with a binary choice between two identical nest-sites. By individually tagging each ant with a unique radio-frequency identification microchip, and then recording all ant-to-ant 'tandem runs'-stereotyped physical interactions that communicate information about potential nest-sites-we assembled the networks that trace the spread of consensus throughout the colony. Through repeated emigrations, we show that both the order in which these networks are assembled and the position of each individual within them are consistent from emigration to emigration. We demonstrate that the formation of the consensus is delegated to an influential but exclusive minority of highly active individuals-an 'oligarchy'-which is further divided into two subgroups, each specialized upon a different tandem running role. Finally, we show that communication primarily occurs between subgroups not within them, and further, that such between-group communication is more efficient than within-group communication.

Short-term activity cycles impede information transmission in ant colonies.

Rhythmical activity patterns are ubiquitous in nature. We study an oscillatory biological system: collective activity cycles in ant colonies. Ant colonies have become model systems for research on biological networks because the interactions between the component parts are visible to the naked eye, and because the time-ordered contact network formed by these interactions serves as the substrate for the distribution of information and other resources throughout the colony. To understand how the collective activity cycles influence the contact network transport properties, we used an automated tracking system to record the movement of all the individuals within nine different ant colonies. From these trajectories we extracted over two million ant-to-ant interactions. Time-series analysis of the temporal fluctuations of the overall colony interaction and movement rates revealed that both the period and amplitude of the activity cycles exhibit a diurnal cycle, in which daytime cycles are faster and of greater amplitude than night cycles. Using epidemiology-derived models of transmission over networks, we compared the transmission properties of the observed periodic contact networks with those of synthetic aperiodic networks. These simulations revealed that contrary to some predictions, regularly-oscillating contact networks should impede information transmission. Further, we provide a mechanistic explanation for this effect, and present evidence in support of it.