Detecting early signs of depressive and manic episodes in patients with bipolar disorder using the signature-based model

Recurrent major mood episodes and subsyndromal mood instability cause substantial disability in patients with bipolar disorder. Early identification of mood episodes enabling timely mood stabilisation is an important clinical goal. Recent technological advances allow the prospective reporting of mood in real time enabling more accurate, efficient data capture. The complex nature of these data streams in combination with challenge of deriving meaning from missing data mean pose a significant analytic challenge. The signature method is derived from stochastic analysis and has the ability to capture important properties of complex ordered time series data. To explore whether the onset of episodes of mania and depression can be identified using self-reported mood data.Comment: 12 pages, 3 tables, 10 figure

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little of prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (3M:1F), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy controls. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorised as: (i) fugue state, (ii) fugue-to-focal retrograde amnesia, (iii) psychogenic focal retrograde amnesia following a minor neurological episode, and (iv) patients with gaps in their memories. While neurological cases were characterised by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (p=0.012), perhaps reflecting a ‘learning episode’ predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognise the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time-periods, whereas the two focal retrograde amnesia groups showed a ‘reversed’ temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed a lesser improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterised by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch’s and Kopelman’s models of psychogenic amnesia, and with respect to Anderson’s neuroimaging findings in memory inhibition

A decentralized approach to model national and global food and land use systems

The achievement of several sustainable development goals and the Paris Climate Agreement depends on rapid progress towards sustainable food and land systems in all countries. We have built a flexible, collaborative modeling framework to foster the development of national pathways by local research teams and their integration up to global scale. Local researchers independently customize national models to explore mid-century pathways of the food and land use system transformation in collaboration with stakeholders. An online platform connects the national models, iteratively balances global exports and imports, and aggregates results to the global level. Our results show that actions toward greater sustainability in countries could sum up to 1 Mha net forest gain per year, 950 Mha net gain in the land where natural processes predominate, and an increased CO2 sink of 3.7 GtCO2e yr−1 over the period 2020–2050 compared to current trends, while average food consumption per capita remains above the adequate food requirements in all countries. We show examples of how the global linkage impacts national results and how different assumptions in national pathways impact global results. This modeling setup acknowledges the broad heterogeneity of socio-ecological contexts and the fact that people who live in these different contexts should be empowered to design the future they want. But it also demonstrates to local decision-makers the interconnectedness of our food and land use system and the urgent need for more collaboration to converge local and global priorities

Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα and cell-cycle signaling in a breast cancer model

These studies were supported by grants from Cancer Research UK (C503/A5010 and C1938/A6769).Aim : A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation. Methods : The MCF7 breast cancer model is sensitive to estrogens and anti-estrogens while variant lines previously derived from wild-type MCF7 are either relatively 17β-estradiol (E2)-insensitive (LCC1) or fully resistant to estrogen and anti-estrogens (LCC9). Results : In LCC1 and LCC9 cell lines, loss of estrogen sensitivity was accompanied by loss of growth response to transforming growth factor alpha (TGFα), heregulin-beta and pertuzumab. LCC1 and LCC9 cells had enhanced AKT phosphorylation relative to MCF7 which was reflected in downstream activation of phospho-mechanistic target of rapamycin (mTOR), phospho-S6, and phospho-estrogen receptor alpha Ser167 [ERα(Ser167)]. Both AKT2 and AKT3 were phosphorylated in the resistant cell lines, but siRNA knockdown suggested that all three AKT isoforms contributed to growth response. ERα(Ser118) phosphorylation was increased by E2 and TGFα in MCF7, by E2 only in LCC1, but by neither in LCC9 cells. Multiple alterations in E2-mediated cell cycle control were identified in the endocrine-resistant cell lines including increased expression of MYC, cyclin A1, cyclin D1, cyclin-dependent kinase 1 (CDK1), CDK2, and hyperphosphorylated retinoblastoma protein (ppRb), whereas p21 and p27 were reduced. Estrogen modulated expression of these regulators in MCF7 and LCC1 cells but not in LCC9 cells. Seliciclib inhibited CDK2 activation in MCF7 cells but not in resistant variants; in all lines, it reduced ppRb, increased p53 associated responses including p21, p53 up-regulated modulator of apoptosis (PUMA), and p53 apoptosis-inducing protein 1 (p53AIP1), inhibited growth, and produced G2/M block and apoptosis. Conclusions : Multiple changes occur with progression of endocrine resistance in this model with AKT activation contributing to E2 insensitivity and loss of ERα(Ser118) phosphorylation being associated with full resistance. Cell cycle regulation is modified in endocrine-resistant breast cancer cells, and seliciclib is effective in both endocrine-sensitive and resistant diseases.Publisher PDFPeer reviewe

Presacral malakoplakia presenting as foot drop: a case report

Background: Malakoplakia is a rare condition characterized by inflammatory masses with specific histological characteristics. These soft tissue masses can mimic tumors and tend to develop in association with chronic or recurrent infections, typically of the urinary tract. A specific defect in innate immunity has been described. In the absence of randomized controlled trials, management is based on an understanding of the biology and on case reports. Case presentation: Here we describe a case of presacral malakoplakia in a British Indian woman in her late 30s, presenting with complex unilateral foot drop. Four years earlier, she had suffered a protracted episode of intrapelvic sepsis following a caesarean delivery. Resection of her presacral soft tissue mass was not possible. She received empiric antibiotics, a cholinergic agonist, and ascorbic acid. She responded well to medical management both when first treated and following a recurrence of symptoms after completing an initial 8 months of therapy. Whole exome sequencing of the patient and her parents was undertaken but no clear causal variant was identified. Conclusions: Malakoplakia is uncommon but the diagnosis should be considered where soft tissue masses develop at the site of chronic or recurrent infections. Obtaining tissue for histological examination is key to making the diagnosis. This case suggests that surgical resection is not always needed to achieve a good clinical and radiological outcome

Paediatric differentiated thyroid carcinoma: a UK National Clinical Practice Consensus Guideline

This guideline is written as a reference document for clinicians presented with the challenge of managing paediatric patients with differentiated thyroid carcinoma up to the age of 19 years. Care of paediatric patients with differentiated thyroid carcinoma differs in key aspects from that of adults, and there have been several re cent developments in the care pathways for this condition; this guideline has sought to identify and attend to these areas. It addresses the presentation, clinical assessment, diagnosis, management (both surgical and medical), genetic counselling, follow-up and prognosis of affected patients. The guideline development group formed of a multi-disciplinary panel of sub-speciality experts carried out a systematic primary literature review and Delphi Consensus exercise. The guideline was developed in accordance with The Appraisal of Guidelines Research and Evaluation Instrument II criteria, with input from stakeholders including charities and patient groups. Based on scientific evidence and expert opinion, 58 recommendations have been collected to produce a clear, pragmatic set of manage ment guidelines. It is intended as an evidence base for future optimal management and to improve the quality of clinical care of paediatric patients with differentiated thyroid carcinoma

Acute Resistance Exercise Influences Bioelectrical Impedance Analysis Segmental Fat Mass Estimates

Bioelectrical impedance analysis (BIA) is an attractive tool for routine assessment of human body composition. However, there is also concern regarding how some variables, particularly exercise, may affect its measurements and therefore limit the conditions under which this technology can provide useful body composition data. PURPOSE: The purpose of this study was to determine if acute, localized resistance exercise (RE) compromises the validity of BIA segmental fat mass (FM) estimates. METHODS: In a crossover design, 32 healthy, resistance trained adults (18 F, 14 M; age: 23.4 ± 2.3 y; height: 172.4 ± 8.7 cm; body mass: 74.9 ± 15.3 kg; body fat: 25.6 ± 8.4%) completed three conditions in a randomized order: lower-body resistance exercise (L), upper-body resistance exercise (U), and rest (R). The RE protocol included a warm-up consisting of 2 sets of 12-15 repetitions of 3 upper-body exercises (U), or 3 lower-body exercises (L), followed by 5 sets of 10 repetitions per exercise, with 1-minute rest intervals. The R condition involved no exercise. BIA (InBody 770) was completed immediately pre- and post-exercise and at 15-, 30-, and 60-minutes post-exercise. The effects of the acute RE session on BIA estimates of total and segmental FM were analyzed using linear mixed-effects models with condition and time specified as within-subject factors and a random intercept for participant. In all models, the reference groups were R for condition and the pre-exercise time point for time. RESULTS: Condition by time interactions were observed for total and segmental FM. Examination of model coefficients indicated that most condition by time interactions were attributable to differences in the U condition across time relative to the reference group (i.e., R condition at baseline). In relation to the reference group, mean decreases of 0.75 to 1.25 kg for total FM, 0.38 to 0.58 kg for trunk FM, 0.27 to 0.47 kg for leg FM, and 0.15 to 0.22 kg for arm FM were observed in the U condition (p≤0.001 for all). In contrast, no changes across time were observed in the L condition. CONCLUSION: These findings suggest that an acute bout of localized RE influences BIA total and segmental FM estimates to an extent that can compromise accurate interpretation of the results. These data corroborate the need for a period of rest from physical activity, particularly upper body RE, prior to BIA body composition assessment

Modelling Human-Fire Interactions: Combining Alternative Perspectives and Approaches

Although it has long been recognised that human activities affect fire regimes, the interactions between humans and fire are complex, imperfectly understood, constantly evolving, and lacking any kind of integrative global framework. Many different approaches are used to study human-fire interactions, but in general they have arisen in different disciplinary contexts to address highly specific questions. Models of human-fire interactions range from conceptual local models to numerical global models. However, given that each type of model is highly selective about which aspects of human-fire interactions to include, the insights gained from these models are often limited and contradictory, which can make them a poor basis for developing fire-related policy and management practices. Here, we first review different approaches to modelling human-fire interactions and then discuss ways in which these different approaches could be synthesised to provide a more holistic approach to understanding human-fire interactions. We argue that the theory underpinning many types of models was developed using only limited amounts of data and that, in an increasingly data-rich world, it is important to re-examine model assumptions in a more systematic way. All of the models are designed to have practical outcomes but are necessarily simplifications of reality and as a result of differences in focus, scale and complexity, frequently yield radically different assessments of what might happen. We argue that it should be possible to combine the strengths and benefits of different types of model through enchaining the different models, for example from global down to local scales or vice versa. There are also opportunities for explicit coupling of different kinds of model, for example including agent-based representation of human actions in a global fire model. Finally, we stress the need for co-production of models to ensure that the resulting products serve the widest possible community