Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.

Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging.

A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an in situ polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell-interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.

Organization of the human intestine at single-cell resolution.

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.

Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction.

Multiparameter tissue imaging enables analysis of cell-cell interactions in situ, the cellular basis for tissue structure, and novel cell types that are spatially restricted, giving clues to biological mechanisms behind tissue homeostasis and disease. Here, we streamlined and simplified the multiplexed imaging method CO-Detection by indEXing (CODEX) by validating 58 unique oligonucleotide barcodes that can be conjugated to antibodies. We showed that barcoded antibodies retained their specificity for staining cognate targets in human tissue. Antibodies were visualized one at a time by adding a fluorescently labeled oligonucleotide complementary to oligonucleotide barcode, imaging, stripping, and repeating this cycle. With this we developed a panel of 46 antibodies that was used to stain five human lymphoid tissues: three tonsils, a spleen, and a LN. To analyze the data produced, an image processing and analysis pipeline was developed that enabled single-cell analysis on the data, including unsupervised clustering, that revealed 31 cell types across all tissues. We compared cell-type compositions within and directly surrounding follicles from the different lymphoid organs and evaluated cell-cell density correlations. This sequential oligonucleotide exchange technique enables a facile imaging of tissues that leverages pre-existing imaging infrastructure to decrease the barriers to broad use of multiplexed imaging.

Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Lipase-Catalyzed Poly(glycerol-1,8-octanediol-sebacate): Biomaterial Engineering by Combining Compositional and Crosslinking Variables.

This study examined poly(glycerol-1,8-octanediol-sebacate) (PGOS) copolymers with low-level substitution of O (1,8-octanediol) for G (glycerol) units (G/O ratios 0.5:0.5, 0.66:0.33, 0.75:0.25, 0.8:0.2, and 0.91:0.09) prepared in bulk by immobilized Candida antarctica Lipase B (N435) catalysis. The central question explored was the extent that exchanging less than half of poly(glycerol sebacate) (PGS) glycerol units with 1,8-octanediol can be used as a strategy to fine-tune biomaterial properties. Synthesized copolymers having G/O ratios of 0.66:0.33, 0.75:0.25, 0.8:0.2, and 0.91:0.09 have similar molecular weights, where Mw varied from 52,800 to 63,800 g/mol, Mn varied from 5100 to 6450 g/mol, and DM (molecular mass dispersity, Mw/Mn) values were also similar (8.4-11.4). All of the copolymers were branched, and dendritic glycerol units reached 11% for PGOS-0.91:0.09:1.0. Analysis of DSC second heating scans revealed that copolymers with higher 1,8-octanediol contents have relatively higher Tm and ΔHf values. Over the copolymer compositional range studied herein, Tm and ΔHf values varied from 5.3 to 21.1 °C and 8.0 to 23.1 J/g, respectively. Stress-strain curves of PGOS copolymers cured at 140 °C for 48 h exhibited either a unimodal, bimodal, or trimodal response to tensile loading. Varying G/O from 10:1 to 2:1 resulted in significant increases in the peak stress (0.26-4.01 MPa), preyield modulus (0.65-62.59 MPa), failure to strain (64-110%), and failure toughness (0.1-0.56 MPa). This demonstrates that altering the G/O ratio over a narrow compositional range provides biomaterials with widely different yet tunable mechanical properties. Further investigation of PGOS-0.75:0.25:1.0 films revealed that varying the cure conditions from 120 to 160 °C for periods of 24-72 h provides access to biomaterials with a failure strain range from 15 to 224% and Young's modulus from 1.17 to 10.85 MPa. Hence, using the dual variables of compositional variation and changes in cure conditions provides an exciting platform for PGS analogues to optimize material-tissue interactions. Increased contents of 1,8-octanediol slowed in vitro degradation. Slowed degradation of PGOS relative to PGS will be valuable for use in slower healing wounds.

Longitudinal patterns of neuroendocrine coupling from middle childhood to early adolescence.

Recent scholarship has highlighted the importance of understanding relations between hormones, rather than studying hormones in isolation. Considering neuroendocrine coupling, or the coordination of hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis hormones over time, is one way to investigate how systems governing stress responsiveness and pubertal development covary during critical periods. To date, however, most work has considered hormone coupling cross-sectionally. The current study investigated neuroendocrine coupling in a longitudinal sample from the Northeastern United States. Youth (N = 437, 53% male, 90% White) provided saliva samples for analysis of diurnal hormone activity at ages 9 (three samples per day across 3 days) and 12 (one sample per day on the same weekday for 4 weeks). At both timepoints, samples collected 30-min after waking were assayed for cortisol, dehydroepiandrosterone (DHEA), and testosterone. Multilevel growth modeling was used to determine how levels of morning cortisol changed in tandem with DHEA and testosterone. Morning cortisol-DHEA coupling varied by child sex, as males' cortisol-DHEA diminished over time, especially among pubertally advanced males. Females, in contrast, demonstrated strengthening cortisol-DHEA coupling over time, especially more pubertally advanced females. Morning cortisol-testosterone coupling did not vary by sex or pubertal status, demonstrating strengthening associations between ages 9 and 12. The current findings contribute to the literature on hormone coupling across development and expand this work into an earlier developmental phase than previously investigated.

Barriers and facilitators to the administration of prehospital tranexamic acid: a paramedic interview study using the theoretical domains framework.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug used to prevent bleeding. It was introduced as an intervention for post-traumatic haemorrhage across emergency medical services (EMS) in the UK during 2012. However, despite strong evidence of effectiveness, prehospital TXA administration rates are low. This study used the theoretical domains framework (TDF) to identify barriers and facilitators to the administration of TXA to trauma patients by EMS providers (paramedics) in the UK. METHODS: Interviews were completed with 18 UK paramedics from a single EMS provider organisation. A convenience sampling approach was used, and interviews continued until thematic saturation was reached. Semistructured telephone interviews explored paramedics' experiences of administering TXA to trauma patients, including identifying whether or not patients were at risk of bleeding. Data were analysed inductively using thematic analysis (stage 1). Themes were mapped to the theoretical domains of the TDF to identify behavioural theory-derived barriers and facilitators to the administration of TXA to trauma patients (stage 2). Belief statements were identified and assessed for importance according to prevalence, discordance and evidence base (stage 3). RESULTS: Barriers and facilitators to paramedics' administration of TXA to trauma patients were represented by 11 of the 14 domains of the TDF. Important barriers included a lack of knowledge and experience with TXA (Domain: Knowledge and Skills), confusion and restrictions relating to the guidelines for TXA administration (Domain: Social/professional role and identity), a lack of resources (Domain: Environmental context and resources) and difficulty in identifying patients at risk of bleeding (Domain: Memory, attention and decision processes). CONCLUSIONS: This study presents a behavioural theory-based approach to identifying barriers and facilitators to the prehospital administration of TXA to trauma patients in the UK. It identifies multiple influencing factors that may serve as a basis for developing an intervention to increase prehospital administration of TXA.

Temperature measurement of babies born in the pre-hospital setting: analysis of ambulance service data and qualitative interviews with paramedics.

BACKGROUND: Birth before arrival at hospital (BBA) is associated with unfavourable perinatal outcomes and increased mortality. An important risk factor for mortality following BBA is hypothermia, and emergency medical services (EMS) providers are well placed to provide warming strategies. However, research from the UK suggests that EMS providers (paramedics) do not routinely record neonatal temperature following BBA. This study aimed to determine the proportion of cases in which neonatal temperature is documented by paramedics attending BBAs in the South West of England and to explore the barriers to temperature measurement by paramedics. METHODS: A two-phase multi-method study. Phase I involved an analysis of anonymised data from electronic patient care records between 1 February 2017 and 31 January 2020 in a single UK ambulance service, to determine 1) the frequency of BBAs attended and 2) the percentage of these births where a neonatal temperature was recorded, and what proportion of these were hypothermic. Phase II involved interviews with 20 operational paramedics from the same ambulance service, to explore their experiences of, and barriers and facilitators to, neonatal temperature measurement and management following BBA. RESULTS: There were 1582 'normal deliveries' attended by paramedics within the date range. Neonatal temperatures were recorded in 43/1582 (2.7%) instances, of which 72% were below 36.5°C. Data from interviews suggested several barriers and potential facilitators to paramedic measurement of neonatal temperature. Barriers included unavailable or unsuitable equipment, prioritisation of other care activities, lack of exposure to births, and uncertainty regarding responsibilities and roles. Possible facilitators included better equipment, physical prompts, and training and awareness-raising around the importance of temperature measurement. CONCLUSIONS: This study demonstrates a lack of neonatal temperature measurement by paramedics in the South West following BBA, and highlights barriers and facilitators that could serve as a basis for developing an intervention to improve neonatal temperature measurement.

Factors influencing conveyance of older adults with minor head injury by paramedics to the emergency department: a multiple methods study.

BACKGROUND: Head injury (HI) in older adults due to low-energy falls result in a substantial number of emergency department (ED) attendances. However, mortality associated with minor HI is very low. Reducing conveyance to hospital is important for older adults and is a priority for the National Health Service (NHS). Therefore, paramedics are required to make accurate decisions regarding conveyance to the ED. This study used routine data and semi-structured interviews to explore the factors that influence paramedic decision-making when considering whether to convey an adult aged 65 years and over with a minor HI to the ED. METHODS: Semi-structured telephone interviews were completed with ten UK paramedics from a single EMS (ambulance) provider organisation. Interviews explored the factors influencing the paramedics' conveyance decision-making in adults aged 65 years and over with a minor HI. Data were initially analysed inductively to develop a thematic framework. A retrospective analysis of ambulance service data was also completed to determine the scope and scale of the issue in Southwest England. An in-depth audit of 100 conveyed patient records was used to determine the proportion of patients conveyed to the ED who met National Institute for Health and Care Excellence (NICE) and Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines. RESULTS: In 2019 South Western Ambulance Service NHS Foundation Trust (SWASFT) attended 15,650 emergency calls to patients aged 65 and over with minor HI, with 70.5% conveyed to ED. 81% of conveyed patients met NICE and JRCALC guideline criteria for conveyance, with the remainder conveyed due to wound care or other medical concerns. The framework developed from the interviews comprised four themes: resources; patient factors; consequences; paramedic factors. Important factors included: the patient's social situation; guidelines; clinical support availability; the history and presentation of the patient; risk. CONCLUSION: This study examined paramedic conveyance decisions for older people with minor HI. It identified multiple influencing factors, highlighting the complex nature of these decisions, and may serve as a basis for developing an intervention to safely decrease ED conveyance in this patient group.

End-of-Life Nursing Education in US Baccalaureate Degree Nursing Programs.

ABSTRACT: End-of-life (EOL) education in baccalaureate nursing degree programs is critical to prepare nurses to care for patients and families with complex physical and psychosocial needs at the EOL. This quantitative descriptive study examines the current state of EOL education in baccalaureate nursing programs across the United States. Results of this study show that nurse educators continue to use strategies to provide this education; however, the amount and frequency of content delivered require improvement, and support for faculty development is needed.

Developmental pathways from preschool irritability to multifinality in early adolescence: the role of diurnal cortisol.

BACKGROUND: Early irritability predicts a broad spectrum of psychopathology spanning both internalizing and externalizing disorders, rather than any particular disorder or group of disorders (i.e. multifinality). Very few studies, however, have examined the developmental mechanisms by which it leads to such phenotypically diverse outcomes. We examined whether variation in the diurnal pattern of cortisol moderates developmental pathways between preschool irritability and the subsequent emergence of internalizing and externalizing symptoms 9 years later. METHOD: When children were 3 years old, mothers were interviewed about children's irritability and completed questionnaires about their children's psychopathology. Six years later, children collected saliva samples at wake-up and bedtime on three consecutive days. Diurnal cortisol patterns were modeled as latent difference scores between evening and morning samples. When children were approximately 12 years old, mothers again completed questionnaires about their children's psychopathology. RESULTS: Among children with higher levels of irritability at age 3, a steeper diurnal cortisol slope at age 9 predicted greater internalizing symptoms and irritability at age 12, whereas a blunted slope at age 9 predicted greater externalizing symptoms at age 12, adjusting for baseline and concurrent symptoms. CONCLUSION: Our results suggest that variation in stress system functioning can predict and differentiate developmental trajectories of early irritability that are relatively more internalizing v. those in which externalizing symptoms dominate in pre-adolescence.

Covariance Between Parent and Child Symptoms Before and During the COVID-19 Pandemic.

OBJECTIVE: COVID-19 has had unprecedented effects on American families, including increases in depression, anxiety, and irritability for both parents and children. While parents and children influence each other's psychological functioning during non-disaster times, this effect may be amplified during times of disaster. The current study investigated how COVID-19 influenced covariance of depressive symptoms and irritability in children and their parents. METHODS: Three hundred and ninety-one parents and their 8- to 17-year-old children (Mage = 10.68 years old, 70% male, 86% White) from a large sample of children and parents, primarily from Southeastern Louisiana, completed self-report measures of depression and irritability approximately 6 weeks into the COVID-19 pandemic, as well as providing retrospective reports of their symptoms prior to the pandemic. Actor-partner interdependence models were used to measure the reciprocal effects of parent symptoms on children and vice versa, both before and during the pandemic. RESULTS: Actor effects in both the depressive symptoms and irritability models suggested that pre-COVID-19 depressive symptoms and irritability were robust predictors of early-COVID-19 depressive symptoms and irritability for both parents and children. Partner effects were also detected in the irritability model, in that parental irritability prior to COVID-19 was associated with decreased child irritability during the pandemic. Both before and during the pandemic, associations between parent and child depressive symptoms and irritability scores were weaker in families evidencing greater dysfunction. CONCLUSIONS: Results suggest that COVID-19-related stress is associated with increases in both parent and child symptomatology, and that family relationships likely influence associations between these symptoms.

Macphatics and PoEMs in Postpartum Mammary Development and Tumor Progression.

Postpartum mammary gland involution is a mammalian tissue remodeling event that occurs after pregnancy and lactation to return the gland to the pre-pregnant state. This event is characterized by apoptosis and lysosomal-mediated cell death of the majority of the lactational mammary epithelium, followed by remodeling of the extracellular matrix, influx of immune cell populations (in particular, T helper cells, monocytes, and macrophages), and neo-lymphangiogenesis. This postpartum environment has been shown to be promotional for tumor growth and metastases and may partially account for why women diagnosed with breast cancer during the postpartum period or within 5 years of last childbirth have an increased risk of developing metastases when compared to their nulliparous counterparts. The lymphatics and macrophages present during mammary gland involution have been implicated in promoting the observed growth and metastasis. Of importance are the macrophages, which are of the "M2" phenotype and are known to create a pro-tumor microenvironment. In this report, we describe a subset of postpartum macrophages that express lymphatic proteins (PoEMs) and directly interact with lymphatic vessels to form chimeric vessels or "macphatics". Additionally, these PoEMs are very similar to tumor-associated macrophages that also express lymphatic proteins and are present at the sites of lymphatic vessels where tumors escape the tissue and enter the lymphatic vasculature. Further characterizing these PoEMs may offer insight in preventing lymphatic metastasis of breast cancer, as well as provide information for how developmental programming of lymphatic endothelial cells and macrophages can contribute to different disease progression.

Development of bipolar disorder and other comorbidity among youth with attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In the Longitudinal Assessment of Manic Symptoms (LAMS) study, 531 of 685 children age 6-12 (most selected for scores > 12 on General Behavior Inventory 10-item Mania scale) had ADHD, 112 with BPSD, and 419 without. With annual assessments for 8 years, retention averaged 6.2 years. Chi-square analyses compared rate of new BPSD and other comorbidity between those with versus without baseline ADHD and between retained versus resolved ADHD diagnosis. Cox regression tested factors influencing speed of BPSD onset. RESULTS: Of 419 with baseline ADHD but not BPSD, 52 (12.4%) developed BPSD, compared with 16 of 110 (14.5%) without either baseline diagnosis. Those who developed BPSD had more nonmood comorbidity over the follow-up than those who did not develop BPSD (p = .0001). Of 170 who still had ADHD at eight-year follow-up (and not baseline BPSD), 26 (15.3%) had developed BPSD, compared with 16 of 186 (8.6%) who had ADHD without BPSD at baseline but lost the ADHD diagnosis (χ2  = 3.82, p = .051). There was no statistical difference in whether ADHD persisted or not across new BPSD subtypes (χ2  = 1.62, p = .446). Of those who developed BPSD, speed of onset was not significantly related to baseline ADHD (p = .566), baseline anxiety (p = .121), baseline depression (p = .185), baseline disruptive behavior disorder (p = .184), age (B = -.11 p = .092), maternal mania (p = .389), or paternal mania (B = .73, p = .056). Those who started with both diagnoses had more severe symptoms/impairment than those with later developed BPSD and reported having ADHD first. CONCLUSIONS: In a cohort selected for symptoms of mania at age 6-12, baseline ADHD was not a significant prospective risk factor for developing BPSD. However, persistence of ADHD may marginally mediate risk of BPSD, and early comorbidity of both diagnoses increases severity/impairment.

Excitation of Cortical nNOS/NK1R Neurons by Hypocretin 1 is Independent of Sleep Homeostasis.

We have proposed that cortical nNOS/NK1R interneurons have a role in sleep homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in cortical nNOS/NK1R cells. Therefore, we investigated whether Hcrt neuron stimulation affects cingulate cortex nNOS/NK1R neurons. Bath application of HCRT1/orexin-A evoked an inward current and membrane depolarization in most nNOS/NK1R cells which persisted in tetrodotoxin; optogenetic stimulation of Hcrt terminals expressing channelrhodopsin-2 confirmed these results, and pharmacological studies determined that HCRTR1 mediated these responses. Single-cell RT-PCR found Hcrtr1 mRNA in 31% of nNOS/NK1R cells without any Hcrtr2 mRNA expression; immunohistochemical studies of Hcrtr1-EGFP mice confirmed that a minority of nNOS/NK1R cells express HCRTR1. When Hcrt neurons degenerated in orexin-tTA;TetO DTA mice, the increased EEG delta power during NREM sleep produced in response to 4 h sleep deprivation and c-FOS expression in cortical nNOS/NK1R cells during recovery sleep were indistinguishable from that of controls. We conclude that Hcrt excitatory input to these deep layer cells is mediated through HCRTR1 but is unlikely to be involved in the putative role of cortical nNOS/NK1R neurons in sleep homeostasis.

Associations between Parental Psychopathology and Sexual Behavior in an Outpatient Psychiatric Sample.

Early age of sexual debut is associated with an increase in negative outcomes, including higher incidence of nonconsensual sexual experiences, higher rates of sexually transmitted infections, and risky sexual practices. Little research has examined the role of parental psychopathology as a predictor of adolescent sexual activity, however. The current study aims to close this gap by examining the relationship between parental psychopathology and sexual activity in a longitudinal sample of youth. Participants were 685 adolescents from the Longitudinal Assessment of Manic Symptoms study, the majority of whom were male (67%) and White (65%). Analyses considering likelihood of sexual initiation included the full sample, whereas analyses considering predictors of the age of sexual debut included the 162 participants who reported ever having sexual intercourse (62% male, 51% White) via the Youth Risk Behavior Surveillance-High School version. Cox regression analyses suggested that maternal generalized anxiety disorder predicted decreased likelihood of initiating sex during the 8-year follow-up period, whereas paternal conduct disorder predicted increased likelihood of initiating sex. Multivariate linear regressions also showed that maternal conduct disorder predicted earlier age of sexual debut among those who had initiated, whereas paternal antisocial personality disorder predicted later age of sexual debut. These associations were observed in both male and female adolescents. Furthermore, these effects were largely not explained by the established relationship between youth psychopathology and sexual behavior. Results have implications for interventions aimed at decreasing sexual risk taking in vulnerable youth.

A qualitative study on conveyance decision-making during emergency call outs to people with dementia: the HOMEWARD project.

BACKGROUND: Paramedics are increasingly required to make complex decisions as to whether they should convey a patient to hospital or manage their condition at the scene. Dementia can be a significant barrier to the assessment process. However, to our knowledge no research has specifically examined the process of decision-making by paramedics in relation to people with dementia. This qualitative study was designed to investigate the factors influencing the decision-making process during Emergency Medical Services (EMS) calls to older people with dementia who did not require immediate clinical treatment. METHODS: This qualitative study used a combination of observation, interview and document analysis to investigate the factors influencing the decision-making process during EMS calls to older people with dementia. A researcher worked alongside paramedics in the capacity of observer and recruited eligible patients to participate in case studies. Data were collected from observation notes of decision-making during the incident, patient care records and post incident interviews with participants, and analysed thematically. FINDINGS: Four main themes emerged from the data concerning the way that paramedics make conveyance decisions when called to people with dementia: 1) Physical condition; the key factor influencing paramedics' decision-making was the physical condition of the patient. 2) Cognitive capacity; most of the participants preferred not to remove patients with a diagnosis of dementia from surroundings familiar to them, unless they deemed it absolutely essential. 3) Patient circumstances; this included the patient's medical history and the support available to them. 4) Professional influences; participants also drew on other perspectives, such as advice from colleagues or information from the patient's General Practitioner, to inform their decision-making. CONCLUSION: The preference for avoiding unnecessary conveyance for patients with dementia, combined with difficulties in obtaining an accurate patient medical history and assessment, mean that decision-making can be particularly problematic for paramedics. Further research is needed to find reliable ways of assessing patients and accessing information to support conveyance decisions for EMS calls to people with dementia.