Changes in the numbers of hospital-based abortions and outpatient early medical abortions in Victoria, 2012-22: a retrospective cohort study.

OBJECTIVES: To assess changes in the monthly numbers of hospital-based abortions and outpatient early medical abortions in Victoria during January 2012 - March 2022, with a particular interest in the impact of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: Population-based retrospective cohort study; time series analysis of Victorian Admitted Episodes Dataset (VAED) and Pharmaceutical Benefits Scheme (PBS) data. SETTING, PARTICIPANTS: All admitted care episodes in Victoria during 1 January 2012 - 31 March 2022 with medical abortion as the principal diagnosis; all PBS claims for mifepristone-misoprostol (MS-2 Step) during 1 January 2015 (date of listing) - 31 March 2022. MAIN OUTCOME MEASURES: Changes in monthly numbers (with 95% confidence intervals [CIs]) of admissions for hospital-based and outpatient early medical abortions during the pre-pandemic period (January 2012 - March 2020), the first full month of the COVID-19 pandemic (April 2020), and the pandemic period (May 2020 - March 2022). RESULTS: The monthly number of hospital-based abortions declined in Victoria during the pre-pandemic period (slope, -2.92 [95% CI, -3.45 to -2.38] per month); the rate of decline was greater during the pandemic period (slope, -5.74 [95% CI, -10.5 to -0.96] per month). The monthly number of outpatient early medical abortions increased during the pre-pandemic period (slope, 5.94 [95% CI, 5.34-6.34] per month); it declined during the first month of the pandemic (slope, -26.4 [95% CI, -70.1 to -17.3] per month), but did not significantly change thereafter. The total monthly number of abortions during the pandemic period did not deviate markedly from the pre-pandemic median value. The pre-pandemic declines in monthly numbers of abortions in major city hospitals, in private hospitals, or at earlier than 14 weeks' gestation intensified during the pandemic period. During January 2015 - March 2020, 14 634 of 103 496 abortions were outpatient medical abortions (14%); during the pandemic period, 11 154 of 33 056 abortions were outpatient medical abortions (33%). CONCLUSIONS: The use of outpatient early medical abortion has steadily increased in Victoria since the PBS listing of mifepristone-misoprostol, which helped ensure access to abortion during the COVID-19 pandemic. Outpatient medical abortions may eventually outnumber surgical early abortions in Victoria, but they are not always appropriate: hospitals will continue to be essential for comprehensive abortion care.

The impact of COVID-19 lockdown measures on older residents' social connections and everyday wellbeing within housing schemes that provide care and support in England and Wales.

The COVID-19 pandemic and the lockdown measures imposed as a result affected the lives of people in all parts of society across the world. In 2020, during the first UK national lockdown, older adults (aged 70 years and over) were told to 'shield' within their homes, as they were regarded as being at higher risk of serious COVID-19 infection compared to other age groups. This paper explores older adults' experiences of COVID-19 lockdown measures whilst living in housing with care schemes for older people. The purpose is to examine the impact of the lockdown measures on scheme life including social connections amongst residents and their general everyday wellbeing during this time. We present qualitative findings based on interviews with 72 residents who took part in longitudinal and cross-sectional interviews across 26 housing with care schemes. Data were analysed using a thematic framework approach to examine specifically their experiences of living in housing with care schemes during the 2020 UK lockdown. The paper highlights that COVID-19 restrictions had a detrimental impact on the social connections and interactions of older residents living in housing with care schemes, as well as on their feelings of autonomy and independence. Despite this, residents adapted and coped with self-isolation restrictions and sought out positive ways to maintain social contact with others inside and outside to the scheme. We further highlight the tensions that providers of housing for older adults faced in promoting residents' autonomy and connectedness whilst also trying to provide a safe living environment and protect residents from risk of COVID-19 infection. Our findings apply not only to a pandemic situation but to the broader understanding of how housing with care for older adults must navigate between autonomy and support.

Outcomes of a Large Series of Laparoscopic Ventral Hernia Repairs after Liver Transplantation.

BACKGROUND: The hernia defects that develop in liver transplant recipients tend to be complex. Unfortunately, there is a paucity of data to guide post-transplant hernia management. Our goal was to evaluate the outcomes following laparoscopic ventral hernia repair (LVHR) in liver transplant recipients. METHODS: A retrospective review of a prospectively kept database of liver transplant patients at a single tertiary healthcare facility was completed. All patients between 2007 and 2020 who underwent LVHR for a hernia at their transplant incision site were included. The primary outcome studied was hernia recurrence. Secondary outcomes included time-to-hernia repair, complications, and length of stay (LOS). RESULTS: There were 89 patients who met inclusion criteria. 82% were male, mean age was 60 years, and mean body mass index was 30.2 kg/m2. 94.4% were on tacrolimus and 36% on mycophenolate mofetil. Median time-to-hernia repair was 16 months with a mean mesh size of 743 cm2 and length of stay of 3.7 days. None required conversion to an open operation. Postoperative complications included ileus (20.2%), acute kidney injury (11.2%), pneumonia (6.7%), and bleeding requiring re-operation (1.1%). Hernia-related complications included chronic suture site pain (1.1%), seroma requiring intervention (3.3%), surgical site infection (3.3%), nonoperative mesh infection (1.1%), and mesh infection requiring explantation (1.1%). Median follow-up was 23 months. Hernia recurrence occurred in 4.5% and no predictive variables for recurrence were identified. CONCLUSIONS: Although the hernia defects that develop in liver transplant recipients are complex and their comorbidities significant, LVHR can safely and effectively repair these defects with low rates of recurrence and complications.

SETDB1: A perspective into immune cell function and cancer immunotherapy.

Oncogene SET Domain Bifurcated 1 (SETDB1)/ESET, an H3K9 methyltransferase, was originally discovered over two decades ago; however, its function in the immune response was not first reported until 2011. SETDB1 immune functions include B cell maturation, T cell activity regulation, and immune escape in cancer cells. In B lymphocytes, SETDB1 mediates the transition from pro-B to pre-B cells and represses endogenous retroviruses (ERV) to encourage B cell lineage differentiation and maturation. SETDB1 alters T cell function by methylating IL-2 and IL-17 promoters and mediating T cell lineage commitment and development. In addition, SETDB1 plays a critical role in ERV silencing within a variety of immune cells, which can indirectly weaken the immune response. Although SETDB1 is critical for normal immune cell function, overexpression in cancer cells negatively impacts immune cell fights against cancer through decreased tumour immunogenicity. Within cancer cells, SETDB1 overexpression represses production and infiltration of antitumour immune cells, mediates immune escape through TE and ERV silencing, represses the type I interferon pathway, and interferes in immune checkpoint blockade (ICB) outcomes by regulation of PD-L1 expression and IFN signalling. In this review, we further discuss the immunological mechanisms of SETDB1 in normal and cancerous cells and its implications in cancer immunotherapy.

The costs of care: An ethnography of care work in residential homes for older people.

The cost of social care, the work conditions experienced by care workers and the quality of care provided by residential homes for older people are all linked, yet we know very little about how this relationship works in practice. Drawing upon an ethnography of two differently priced residential care homes for older people in Southern England, I examine the implications of different financial regimes for care-giving practices. I show how the scheduling and allocation of resources-conveyed, for example, in formal routines and staffing levels-structure the care workers' time, tasks and activities in each setting. This acts to symbolically demarcate what, or who, is valued. I argue that the availability of resources facilitates and impedes the symbolic culture of care work, shapes care workers' ability to afford dignity to the individuals in their care and affects how care workers experience, and relate to, their labour. I conclude by discussing how current practices of funding and pricing social care have effects seeping beyond the practical and measurable, and into the realm of the symbolic.

Genome Sequences of Subcluster M2 Mycobacteriophages Estes and Aziz.

Estes and Aziz are mycobacteriophages that were isolated on Mycolicibacterium smegmatis mc2155 at room temperature from soil samples collected in Spokane, WA. Their genome sequences are 83,601 and 83,412 bp long, respectively, and they are members of subcluster M2. Each contains 21 tRNA genes and short conserved repeats characteristic of cluster M phages.

Can extra care housing support the changing needs of older people living with dementia?

With over two-thirds of people with dementia living in the community and one-third of those living alone, it is important to consider the future housing needs of this population, particularly as symptoms of cognitive impairment increase. Policy in England has focused on enabling people living with dementia to remain in their own homes for as long as possible, often with the support of a family carer. However, many people struggle to maintain an acceptable quality of life in their own homes as their dementia advances, often due to the design limitations of mainstream housing and the challenge of finding specialist domiciliary care that is affordable and of sufficient quality. Extra care housing offers a model that aims to support older people living in their own apartments, whilst also offering specialist person-centred care as and when it is needed. This paper reports on a longitudinal project that explored how extra care housing can respond to the changing social care needs of residents, including those living with dementia. Participants included residents and staff from four extra care housing schemes, one of which was a specialist dementia scheme, in two regions of England. Interviews were carried with 51 residents across 4 rounds at 5 month intervals between October 2015 and June 2017. Interviews were also carried out with 7 managers, 20 care staff and 2 local authority commissioners of housing for older people. Key factors included person-centred care and support, flexible commissioning and staffing, appropriate design of the environment and suitable location of the scheme within the wider community. The challenge of delivering services that addresses these issues during a period of reduced public spending is acknowledged. Further research is suggested to compare different approaches to supporting people with dementia, including integrated and separated accommodation, and different stages of dementia.

Long-Term Intranasal Insulin Aspart: A Profile of Gene Expression, Memory, and Insulin Receptors in Aged F344 Rats.

Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin's efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

'You have got to stick to your times': Care workers and managers' experiences of working in extra care housing.

Extra care housing (ECH) has been lauded as an innovative model of housing with care for older people that promotes and supports independent living. The study used a qualitative design to explore how care is delivered in four extra care settings in England over 20 months during 2016-2017. This paper reports findings from semi-structured interviews with 20 care workers and seven managers. The article argues that, despite being heralded as a new model, care workers in ECH face similar organisational pressures as those working in more conventional settings and, in turn, the care which they are able to provide to residents mimics traditional forms of care.

Isolating Rare Cells and Circulating Tumor Cells with High Purity by Sequential eDAR.

Isolation and analysis of circulating tumor cells (CTCs) from the blood of patients at risk of metastatic cancers is a promising approach to improving cancer treatment. However, CTC isolation is difficult due to low CTC abundance and heterogeneity. Previously, we reported an ensemble-decision aliquot ranking (eDAR) platform for the rare cell and CTC isolation with high throughput, greater than 90% recovery, and high sensitivity, allowing detection of low surface antigen-expressing cells linked to metastasis. Here we demonstrate a sequential eDAR platform capable of isolating rare cells from whole blood with high purity. This improvement in purity is achieved by using a sequential sorting and flow stretching design in which whole blood is sorted and fluid elements are stretched using herringbone features and the parabolic flow profile being sorted a second time. This platform can be used to collect single CTCs in a multiwell plate for downstream analysis.

Infant skin care: updates and recommendations.

PURPOSE OF REVIEW: Neonatal skin acclimates rapidly to dry, aerobic conditions at birth and skin function gradually matures throughout infancy. Gentle skin care practices support the ongoing development and function of newborn skin. This article reviews research updates and current skin care recommendations for full-term infants, premature infants, and infants born with severe cutaneous manifestations of genetic skin disorders. RECENT FINDINGS: Although safe early bathing of full-term infants with environmental controls is possible, delaying the first newborn bath for 12-24 h of life offers benefits of increased parental bonding and breastfeeding success. Swaddled bathing every 4 days is an effective bathing strategy for premature neonates. Among infants with a family history of atopic dermatitis, regular application of bland skin moisturizers reduces their risk of developing the disease. For newborns with erosive or blistering genetic skin conditions, use of specialized wound dressings and emollients promotes wound healing and helps limit skin damage. Environmental control with humidified incubators helps prevent life-threatening hypernatremic dehydration among babies born with collodion membranes; however, affected infants can tolerate breaks outside of the humidifier to promote parent-infant bonding. SUMMARY: This article reviews infant skin care recommendations relevant to pediatric practice. Research to further optimize newborn skin care is ongoing, particularly, for the special populations of premature neonates and infants born with severe skin disease.

Using longitudinal qualitative research to explore extra care housing.

PURPOSE: The process of individual ageing in the context of a care environment is marked by continuity and change. It is shaped by individual, health-related factors as well as by diverse social and environmental factors, including characteristics of the places where older people live. The aim of this paper was to explore how longitudinal qualitative research, as a research method, could be used to explore older people's changing care needs. METHODS: The study used a longitudinal design to examine how the care and support needs of residents and their expectations of services developed over time and how these were influenced by changes in the organisation of their housing as well as in the make-up of the resident population. Residents were interviewed on four occasions over 20 months. RESULTS: The study highlighted the complex ways in which some participants proactively managed the care and support they received, which we argue would have been difficult to discern through other methods. CONCLUSION: The study adds to the growing evidence base that supports the use of qualitative longitudinal research; the approach enables the researcher to capture the diverse and mutable nature of older people's experiences at a time of profound change in their lives.

White Matter Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk.

OBJECTIVE: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. METHODS: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluid-attenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slice-based techniques. RESULTS: dWMHs but not pWMHs were increased in patients at high risk of CVD; pWMHs but not dWMHs were associated with decreased regional cortical (GM) blood flow. We also found that blood flow in WM is decreased in regions of both pWMH and dWMH, with a greater degree of decrease in pWMH areas. CONCLUSIONS: WMHs are usefully divided into dWMH and pWMH regions because they demonstrate differential effects. 3-D regional WMH volume is a potentially valuable marker for CVD based on associations with cortical CBF and WM CBF.

Optical painting and fluorescence activated sorting of single adherent cells labelled with photoswitchable Pdots.

The efficient selection and isolation of individual cells of interest from a mixed population is desired in many biomedical and clinical applications. Here we show the concept of using photoswitchable semiconducting polymer dots (Pdots) as an optical 'painting' tool, which enables the selection of certain adherent cells based on their fluorescence, and their spatial and morphological features, under a microscope. We first develop a Pdot that can switch between the bright (ON) and dark (OFF) states reversibly with a 150-fold contrast ratio on irradiation with ultraviolet or red light. With a focused 633-nm laser beam that acts as a 'paintbrush' and the photoswitchable Pdots as the 'paint', we select and 'paint' individual Pdot-labelled adherent cells by turning on their fluorescence, then proceed to sort and recover the optically marked cells (with 90% recovery and near 100% purity), followed by genetic analysis.

Peripheral (deep) but not periventricular MRI white matter hyperintensities are increased in clinical vascular dementia compared to Alzheimer's disease.

BACKGROUND AND PURPOSE: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. METHODS: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. PVH and dWMH were rated separately and independently by two different examiners using the Scheltens scale. Receiver operator characteristic (ROC) curves were generated using logistic regression to assess classification of VAD (13 patients) versus AD (129 patients). Clinical diagnoses were made in a specialty memory disorders clinic. RESULTS: Using PVH rating alone, overall classification (area under the ROC curve, AUC) was 75%, due only to the difference in age between VAD and AD patients in our study and not PVH. In contrast, dWMH rating produced 86% classification accuracy with no independent contribution from age. A global Longstreth rating that combines dWMH and PVH gave an 88% AUC. CONCLUSIONS: Increased dWMH indicate a higher likelihood of VAD versus AD. Assessment of dWMH on MRI scans using Scheltens and Longstreth scales may aid the clinician in distinguishing the two conditions.

Improved detection by ensemble-decision aliquot ranking of circulating tumor cells with low numbers of a targeted surface antigen.

Circulating tumor cells (CTCs) are shed from a solid tumor into the bloodstream and can seed new metastases. CTCs hold promise for cancer diagnosis and prognosis and to increase our understanding of the metastatic process. However, their low numbers in blood and varied phenotypic characteristics make their detection and isolation difficult. One source of heterogeneity among CTCs is molecular: When they leave the primary tumor, these cells must undergo a molecular transition, which increases their mobility and chance of survival in the blood. During this molecular transition, the cells lose some of their epithelial character, which is manifested by the expression of the cell surface antigen known as epithelial cell adhesion molecule (EpCAM). Some tumors shed CTCs that express high levels of EpCAM; others release cells that have a low level of the antigen. Nevertheless, many CTC isolation techniques rely on the detection of EpCAM to discriminate CTCs from other cells in the blood. We previously reported a high-throughput immunofluorescence-based technology that targets EpCAM to rank aliquots of blood for the presence or absence of a CTC. This technology, termed ensemble decision aliquot ranking (eDAR), recovered spiked-in cancer cells (taken from a model EpCAM(high) cell line) from blood at an efficiency of 95%. In this paper, we evaluated eDAR for recovery of cells that have low EpCAM expression and developed an immunofluorescence labeling strategy that significantly enhances the method's performance. Specifically, we used a cocktail of primary antibodies for both epithelial and mesenchymal antigens as well as a dye-linked secondary antibody. The cocktail allowed us to reliably detect a model EpCAM(low) cell line for triple negative breast cancer, MDA-MB-231, with a recovery efficiency of 86%. Most significantly, we observed an average of 6-fold increase in the number of CTCs isolated from blood samples from breast cancer patients. These findings underscore the importance of benchmarking CTC technologies with model cell lines that express both high and low levels of EpCAM.

Negative dielectrophoretic capture and repulsion of single cells at a bipolar electrode: the impact of faradaic ion enrichment and depletion.

This paper describes the dielectrophoretic (DEP) forces generated by a bipolar electrode (BPE) in a microfluidic device and elucidates the impact of faradaic ion enrichment and depletion (FIE and FID) on electric field gradients. DEP technologies for manipulating biological cells provide several distinct advantages over other cell-handling techniques including label-free selectivity, inexpensive device components, and amenability to single-cell and array-based applications. However, extension to the array format is nontrivial, and DEP forces are notoriously short-range, limiting device dimensions and throughput. BPEs present an attractive option for DEP because of the ease with which they can be arrayed. Here, we present experimental results demonstrating both negative DEP (nDEP) attraction and repulsion of B-cells from each a BPE cathode and anode. The direction of nDEP force in each case was determined by whether the conditions for FIE or FID were chosen in the experimental design. We conclude that FIE and FID zones generated by BPEs can be exploited to shape and extend the electric field gradients that are responsible for DEP force.

The business of care: the moral labour of care workers.

Drawing on a case study conducted in a private residential care home, this article examines the emotional labour of care workers in relation to the moral construction of care and the practical experiences of work. An examination of the company's discursive attempts to construct, manage and demarcate its employees' emotional labour was carried out alongside an exploration of the carers' own interpretations of, and enrolment in, the care-giving role. The potential economic and emotional consequences of these occurrences were a key focus of the inquiry. The study found that carers, encouraged by the company, naturalised their emotional labour, and that this had contradictory consequences. On the one hand it justified the economic devaluation of the carer's work and left her vulnerable to emotional over-involvement and client aggression. On the other, it allowed the worker to defend the moral interests of those within her care and to see when those interests were in conflict with the economic motivations of her employer.

New generation of ensemble-decision aliquot ranking based on simplified microfluidic components for large-capacity trapping of circulating tumor cells.

Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method. Using the reported second generation of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false positive rate (n = 15).

Surface nucleated growth of dipeptide fibres.

We report the surface nucleated growth of self-assembled dipeptide films. The seeding-layer was a thin dipeptide film with a globular structure. Placing the seeding-layer in contact with dipeptide led to growth of fibres overnight. Active enzymes were incorporated into the gel by adding them to the growth solution.