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The relationship between preterm birth and postpartum anxiety:A first-in-field systematic review
Get PDFIntroduction: Preterm birth poses substantial risks to infant health and maternal mental health, particularly anxiety. The evidence base for associations between gestational age and postpartum anxiety has yet to be synthesised as a whole. This first-in-field systematic review aimed to investigate the relationship between gestational age at delivery and postpartum anxiety, and explore the experiences of mothers of premature infants with postpartum anxiety.Materials and Methods: Searches were conducted across 10 psychological, clinical, and allied health databases from inception to 6th October 2024 (PROSPERO CRD: CRD42023369647). There were no restrictions on language or study design. Only studies that assessed the relationship between gestational age at delivery, or preterm birth, and maternal anxiety assessed during the first postpartum year were eligible for inclusion in this review. Initial searches were conducted by one author. Identification and data extraction of studies were performed by two different authors independently. Results: Twenty-three studies were eligible for inclusion in the review. All studies were quantitative; no qualitative studies were eligible for inclusion. Data were synthesised via narrative synthesis. Taken together, the results indicate an inverse association between gestational age at delivery (preterm birth) and anxiety. Conclusions: Variable timing of assessment and tool(s) used to measure postpartum anxiety, alongside limited consideration of categories of gestational age (i.e., extremely, very, moderate-to-late preterm) limit the ability to make firm conclusions about the extent of this relationship
Vδ1 T-cell subset appears to be responsive to PD-1 blockade therapy and is associated with survival in melanoma
Get PDFBACKGROUND: Although most studies of anticancer T-cell immunity focus on αβ T cells, γδ T cells are attracting increasing attention due to their involvement in antitumor immune responses in various cancer entities, including melanoma. While immune checkpoint blockade (ICB) using the antagonistic programmed cell death protein 1 (PD-1) antibodies nivolumab and pembrolizumab significantly improved the survival of patients with melanoma with distant metastasis, prognosis remains poor. PD-1 is not only expressed by αβ T cells but also by γδ T cells, making this numerically minor population of unconventional T cells, whose role in melanoma is still elusive, a target of ICB.METHODS: Here, we present a detailed γδ T-cell profiling study in late-stage melanoma at single-cell level using mass and polychromatic flow cytometry, T-cell receptor repertoire analyses and immunohistochemistry.RESULTS: Our analyses link high frequencies of peripheral Vδ1 T cells before the start of anti-PD-1 therapy to a significantly reduced overall survival. In these patients, the Vδ1 compartment is dominated by a late-differentiated senescent-like phenotype that is presumably unresponsive to therapy. This phenotype is less prevalent at the tumor site and analysis of RNA sequencing data revealed that the abundance of Vδ1 T cells within the tumor was positively associated with survival.CONCLUSIONS: Our study suggests that Vδ1 T cells are associated with clinical outcomes, with a responsive subset expanding under ICB in patients where such a response remains possible. The observed clinical effects may be supported by the infiltration of these cells into the tumor, where they contribute to cancer immunosurveillance.</p
Time to lithium:an electronic health records study
No full textBackground: Lithium monotherapy has been recommended as a first-line maintenance or long-term pharmacological therapy for bipolar disorder (BD) by numerous clinical guidelines including the UK National Institute for Health and Care Excellence (NICE guidelines), the British Association for Psychopharmacology (BAP) guidelines and the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines. This is unsurprising given the existing evidence for its efficacy in prophylaxis of mood episodes [1] and prevention of completed suicide in mood disorders [2]. Previous research has linked early lithium use with better outcomes for patients with BD [3]. Despite its extensive evidence as an effective treatment for BD, lithium prescription has declined in the past years [4]. Potential reasons for this decline have been recently studied and include the widespread use of second-generation antipsychotics and a lack of commercial support due to not having a medication patent [5].Objectives: With the present study, our primary aim was to determine the time between the initial assessment with a mental health professional and the initiation of lithium. Secondary objectives included determining the time between first assessment and recorded diagnosis of BD, number of mood episodes experienced by those with BD before lithium was prescribed, predominant mood polarity when lithium was prescribed and number of antipsychotics before lithium was initiated.Methods: Free-text clinical notes were extracted from a de-identified electronic health record database. Inclusion criteria were: a) having an ICD-10 diagnosis of F30 (Manic episode) or F31 (Bipolar affective disorder) recorded between 1 January 2015 and 01 January 2020, b) being aged 18 years on the date of the first recorded F30 or F31 diagnosis, c) having had at least one face-to-face assessment with a medically qualified practitioner, d) receiving treatment with lithium at a therapeutic dose, ascertained by a laboratory recorded lithium serum level above 0.0 mmol/L e) having a continuous first episode of care within SLaM for at least six months during which the F30 or F31 diagnosis was recorded. Exclusion criteria were: a) having any recorded treatment or episode of care outside of SLaM before lithium was prescribed, or b) unclear or incomplete clinical documentation. Data were extracted on 16 February 2021 and free-text clinical notes were chronologically read line-by-line by a psychiatrist. Language processing or other data algorithms were not used.Results: A cohort of 88 patients was identified based on inclusion and exclusion criteria. The median time between the first assessment and prescription of lithium was 588 days. The median time between assessment and diagnosis of BD was 220 days, and patients presented with a median of 2.5 mood episodes and were prescribed a median of 2 antipsychotics prior to lithium prescription. Around 30% of patients presented with manic polarity symptoms at the time of lithium prescription.Conclusions: Our study identified a significant delay between initial assessment with a clinician and the prescription of lithium. In our opinion, interventions are urgently needed to reinforce the prescription of lithium, given its proven efficacy and links to better prognosis
Psychotropic medication and the fetal brain
No full textMedications known to cross the blood–brain barrier (psychotropic medications) are commonly prescribed to women during pregnancy, often for the management of mental illness. Although there is little evidence of gross neurological teratogenicity of any medication in current widespread use, a growing body of evidence from animal models, human magnetic resonance imaging and behavioural studies suggests that more subtle adverse effects on early life neurodevelopment may result from in utero psychotropic exposure. Understanding these consequences is of crucial importance as prescribing rates of psychotropic medication during pregnancy have increased rapidly in recent years. We review current studies directly quantifying early life brain correlates of exposure, discuss plausible mechanistic pathways and make suggestions for future research. (Figure presented.).</p
High-Order CSK Realization for MC via Spatially Distributed Multicellular Consortia
Get PDFProgress in molecular communication (MC) relies on the development of novel and efficient signal processing mechanisms. Synthetic biology meets this need by allowing precise control over intracellular signaling and molecular exchange in engineered cells, enabling engineered signal processing tasks within living networks. Facilitated by this advancement, we design and engineer multicellular consortia with spatial segregation to realize an octuple concentration shift keying (8-CSK) transceiver—covering both modulation and demodulation—in a fully biological framework using simple and reusable single-input single-output cells. The proposed design demonstrates the scalability of our framework while maintaining the advantages of distributed computation, minimal genetic manipulation, and signal orthogonality. Additionally, we derive the mathematical framework of 8-CSK based on modular building blocks, enabling an accurate theoretical characterization of the system. Simulation results from the agent-based simulator—BSim—validate the feasibility of our extended design and demonstrate strong agreement with the theoretical analysis, highlighting the robustness and applicability of our CSK framework to higher-order modulation schemes.</p
Nozick and the Invisible Hand of Racial Injustice
Get PDFContemporary western democracies like the United States and the United Kingdom bear the imprint of historical racial injustice – slavery, segregation, discrimination, and mistreatment and neglect by public authorities. Libertarian political theory might appear well placed to contribute to debates about attaining racial justice, given its emphasis on individual rights and strict limits on state action, but Charles Mills claimed libertarians largely ignored questions of race and often opposed measures aimed at achieving racial justice. This article reexamines Robert Nozick’s Anarchy, State, and Utopia in the light of Mills’ claims. Nozick endorses libertarian beliefs about the ability of free markets to eliminate injustice, the role of the state in creating injustice, and the danger of political projects that propose to engineer a just society, but his work also shows that these beliefs do not exhaust questions of race and racial justice. Analysis of Nozick’s work illuminates the potential for invisible-hand processes to reproduce as well as eliminate injustice, the impossibility of establishing a just starting point for the series of voluntary exchanges that have led to real world holdings of income and wealth, and the fact that injustice concerns more than harms inflicted on specific persons by identifiable individuals. A form of universal basic income may therefore be justified to rectify historical injustices while minimising the risk of future political exploitation
Beyond One-Hot Encoding? Journey Into Compact Encoding for Large Multi-Class Segmentation
Get PDFThis work presents novel methods to reduce computational and memory requirements for medical image segmentation with a large number of classes. We curiously observe challenges in maintaining state-of-the-art segmentation performance with all of the explored options. Standard learning-based methods typically employ one-hot encoding of class labels. The computational complexity and memory requirements thus increase linearly with the number of classes. We propose a family of binary encoding approaches instead of one-hot encoding to reduce the computational complexity and memory requirements to logarithmic in the number of classes. In addition to vanilla binary encoding, we investigate the effects of error-correcting output codes (ECOCs), class weighting, hard/soft decoding, class-to-codeword assignment, and label embedding trees. We apply the methods to the use case of whole brain parcellation with 108 classes based on 3D MRI images. While binary encodings have proven efficient in so-called extreme classification problems in computer vision, we faced challenges in reaching state-of-the-art segmentation quality with binary encodings. Compared to one-hot encoding (Dice Similarity Coefficient (DSC) =82.4(2.8)), we report reduced segmentation performance with the binary segmentation approaches, achieving DSCs in the range from 39.3 to 73.8. Informative negative results all too often go unpublished. We hope that this work inspires future research of compact encoding strategies for large multi-class segmentation tasks.</p
Time to lithium:A case register study of lithium initiation in bipolar disorder
Get PDFBackground:Lithium monotherapy has been recommended as first-line maintenance or long-term pharmacological therapy for bipolar disorder (BD). Previous research has linked early lithium use with better outcomes for people with BD. Despite extensive evidence as an effective treatment for BD, lithium prescribing continues to decline.Aims:Our primary aim was to determine the time between initial assessment by mental health services and lithium initiation in people with BD who were prescribed and concordant with lithium. Secondary objectives included determining the time between the first assessment and recorded BD diagnosis, number of prior mood episodes, polarity when lithium was prescribed and number of antipsychotics before lithium initiation.Methods:Free-text clinical notes were extracted from a de-identified electronic health record database. Eligible records comprised adults with a BD diagnosis who were concordant with lithium treatment.Results:Eighty-eight people were identified, based on inclusion and exclusion criteria. Median time between first assessment and lithium initiation was 659 days. Median time between first assessment and BD diagnosis was 220 days, with a median of 2.5 mood episodes and 2 antipsychotics prescribed prior to lithium. Around 30% of people presented with manic symptoms at the time of lithium prescription. There is a significant delay between first contact with services and initiation of lithium in people with BD.Conclusions:This highlights the potential for earlier intervention with lithium, which could improve outcomes for people with BD