Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.

The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of the vertebrate brain. The polarized epithelia of the CP produce cerebrospinal fluid by transporting water and ions into the ventricles from the blood and normally secrete a large number of proteins. We assessed the feasibility of selective CP transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment of lysosomal storage disease (LSD), a broad category of neurometabolic illness associated with significant burdens to affected patients and their families.

Palliative Care Consults in the Southeast: Lower Readmissions Despite Increased Length of Stay.

: Inpatient palliative care (PC) consultations are increasingly used to address operational challenges. We aimed to understand how PC consultations in a southeastern program, affected by pandemic-related care delays, impacted common clinical performance metrics. : This is a retrospective analysis of a tertiary system's adult patients who received PC consultations from December 2021 to August 2022.

High order expression dependencies finely resolve cryptic states and subtypes in single cell data.

Single cells are typically typed by clustering into discrete locations in reduced dimensional transcriptome space. Here we introduce Stator, a data-driven method that identifies cell (sub)types and states without relying on cells' local proximity in transcriptome space. Stator labels the same single cell multiply, not just by type and subtype, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order gene expression dependencies from a sparse gene-by-cell expression matrix.

Interview Results From a Telehealth Hospice Intervention for Children and Young Adults With Cancer.

Background And Aims: Surveyed families of children and young adults with cancer who participated in a pilot study of three coordinated telehealth visits (triad of patient/family, hospital clinician, and hospice nurse) during the first month of hospice enrollment found telehealth feasible and were highly satisfied with hospice care. The aim of this study is to further explore adult patient and caregiver perspectives on telehealth, specifically the benefits of telehealth, trade-offs with in-person appointments, and the impact on patient care and family end-of-life preparations.

Methods: This is a single-arm prospective pilot study of patients aged 0-29-with cancer initiating hospice care between 2021 and 2022 and their caregivers.

Intracisternal vs intraventricular injection of AAV1 result in comparable, widespread transduction of the dog brain.

Widespread distribution of transduced brain cells following delivery of AAV vectors into the cerebrospinal fluid (CSF) of the cisterna magna (CM) has been demonstrated in large animal brains. In humans, intraventricular injection is preferred to intracisternal injection for CSF delivery due to the risk of brain stem injury. One study in the dog reported adverse reactions to AAV vectors expressing GFP injected into the lateral ventricle but not when injected into the CM.

Paramedic perceptions of barriers and facilitators to the use of ambulance service appropriate care-referral pathways in Northern Ireland: a qualitative study.

Introduction: Paramedic clinical practice has seen significant evolution from the traditional role of transporting patients to an emergency department (ED). An evolving and flexible scope of practice, modernisation and healthcare reform has necessitated the development of a range of referral pathways for paramedics, with the aim of ensuring that service users receive the most appropriate care at the point of contact. Ambulance conveyance rates to EDs in Northern Ireland (NI) have only occasionally fallen below 75%.

The Role of Sex and Gender in Precision Emergency Medicine: A Scoping Review and Proposed Hierarchy.

Background: Precision medicine utilizes individual patient data to guide decision making. Sex and gender medicine is likewise focused on individual patients' biological sex or sociocultural gender as determinants of disease. How these two fields intersect with one another and with acute care medicine is unclear.

Risky hybrid foraging: The impact of risk, reward value, and prevalence on foraging behavior in hybrid visual search.

In hybrid foraging, foragers search for multiple targets in multiple patches throughout the foraging session, mimicking a range of real-world scenarios. This research examines outcome uncertainty, the prevalence of different target types, and the reward value of targets in human hybrid foraging. Our empirical findings show a consistent tendency toward risk-averse behavior in hybrid foraging.

Goals of Surgical Interventions in Youths Receiving Palliative Care.

Importance: Most youths receiving palliative care undergo many surgical interventions over their lifetimes. The intended purposes of interventions in the context of goals of care are not commonly articulated.

Objective: To describe the goals and purposes of surgical intervention in youths receiving palliative care and propose a framework discussing intervention using goal-oriented language.

Childbearing Histories and Midlife Cognition: Accounting for Early Life Factors.

Objectives: Childbearing histories-for example, parity and age at first birth-matter for the health outcomes of mid- and later-life women. There is growing evidence that childbearing may shape cognitive outcomes. However, previous research is not definitive due to its inability to account for selection.

From worries to resilience: a qualitative study of the psychosocial experiences of diverse adolescents and young adults with heart failure and their caregivers.

Background And Objectives: Despite advances in treatment and outcomes for paediatric heart failure, both physical and psychosocial comorbidities remain notable among this patient population. We aimed to qualitatively describe the psychosocial experiences of adolescent and young adults with heart failure and their caregivers' perceptions, with specific focus on personal challenges, worries, coping skills, and resilience.

Methods: Structured, in-depth interviews were performed with 16 adolescent and young adults with heart failure and 14 of their caregivers.

Parents providing palliative care for children with cancer.

Parents of children with cancer provide paediatric palliative care (PPC). However, the activities they perform remain underexplored, especially in low- and middle-income countries (LMICs) where the care heavily relies on family involvement. The aim of this study is to identify parental PPC tasks and intentions to perform PPC tasks and to determine their associated factors.

Plan of Care Visits: Implementation During Hospitalization and Association With 30-Day Readmissions in a Large, Integrated Health Care System.

Background: Plan of Care of Visits (POCV), including the patient, nurse, and hospital provider were implemented across an integrated health system to improve provider-patient communication during hospitalization and patient outcomes.

Objectives: To assess POCV adoption after implementation, patient characteristics assosites were classified as teachsites were classified as teachsites were classified as teachsites were classified as ciated with POCV completion, and association of POCV with 30-day readmissions.

Methods: This retrospective cohort study utilized electronic medical record (EMR) data of 237,430 adult patients discharged to home from 11 hospitals from January 2020 to December 2022.

Parent Views on Parent and Child-reported Outcomes in Pediatric Advanced Cancer: A Qualitative Study.

Background: Research on concurrent parent and patient-reported outcomes has primarily focused on reaching agreement. However, little is known about how to interpret and address discrepancies, which are not uncommon, between both viewpoints.

Objectives: To explore parents' perspectives on reporting about child symptoms and quality of life (QoL) concurrently with their child in the context of pediatric advanced cancer.

No matter what you do, travel is travel in visual foraging.

In visual foraging, foragers collect multiple items from a series of visual displays (or "patches"). When the goal is to maximize the total or the rate of collection of target items, foragers must decide when to leave a depleted patch given that "traveling" from one patch to another incurs a temporal cost. In three experiments, we investigated whether the interposition of a secondary task during travel between patches in visual foraging altered patch-leaving behavior.

Mapping Surgical Intervention Trajectories in Seriously Ill Children Receiving Palliative Care.

Background/purpose: Despite the prevalence of surgical intervention in seriously ill children, data is scarce regarding interventions performed based on type of serious illness. We therefore sought to evaluate the surgical interventions performed from the time of serious illness diagnosis to the present in a cohort of children receiving palliative care, including identification of the surgical specialists involved in these procedures.

Methods: We conducted a retrospective cohort analysis of surgical interventions in 197 children enrolled in a multicenter prospective cohort study (Pediatric Palliative Care Research Network SHARE Study).

Optimizing care pathways: A study of the urgent dispatch program and its impact on emergency department visits.

Introduction: The use of acute hospital-level care at home (hospital-at-home) for patients who are chronically ill has led to decreased medical costs, amount of sedentary time, and hospital admissions. Our large integrated healthcare system identified the need to develop a mechanism through which to decrease emergency department (ED) visits in this patient population by creating a home acute care program called Urgent Dispatch. The primary objective of this study was to determine the medical condition for referral and seven and 30-day ED visit rates.

Categorically distinct subsets allow flexible memory selection in hybrid search.

In many everyday situations, we search our visual surroundings for any one of many memorized items held in memory, a process termed . In some cases, only a portion of the memorized mental list is relevant within a specific visual context, thus, restricting memory search to the relevant subset would be desirable. Previous research had shown that participants largely fail to "partition" memory into several distinct subsets, on a trial-by-trial basis.

Image memorability influences memory for where the item was seen but not when.

Observers can determine whether they have previously seen hundreds of images with more than 80% accuracy. This "massive memory" for WHAT we have seen is accompanied by smaller but still massive memories for WHERE and WHEN the item was seen (spatial & temporal massive memory). Recent studies have shown that certain images are more easily remembered than others (higher "memorability").

In simple but challenging search tasks, most errors are stochastic.

In visual search tasks in the lab and in the real world, people routinely miss targets that are clearly visible: so-called look but fail to see (LBFTS) errors. If search displays are shown to the same observer twice, we can ask about the probability of joint errors, where the target is missed both times. If errors are "deterministic," then the probability of a second error on the same display-given that the target was missed the first time-should be high.