Real-world data to support post-market safety and performance of embolization coils: evidence generation from a medical device manufacturer and data institute partnership.

Background: Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up.

The ALSPAC fetal and neonatal resource: detailed data abstracted from the clinical records of the new-born.

In a previous Data Note, we outlined the data obtained from clinical obstetric records concerning many details of the pregnancies resulting in the births of the children in the Avon Longitudinal Study of Parents and Children (ALSPAC). Here we describe the data that have been abstracted from medical records concerning the fetus and neonate. Full details concerning the selection biases regarding the data abstracted are outlined in the previous Data Note.

Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage.

Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Dsup in reduces oxidative DNA damage and extends the lifespan of budding yeast exposed to chronic oxidative genotoxicity.

ALSPAC parents' descriptions of childhood stresses in their parents and grandparents.

There is evidence that childhood stresses or traumas influence individuals' descendants' health and wellbeing through epigenetic mechanisms. However, few longitudinal studies have details of such ancestral data. Nearly 7,000 parents of the original Avon Longitudinal Study of Parents and Children (ALSPAC) cohort completed questionnaires concerning their parents' and grandparents' childhoods.

Outcomes After Laparoscopic Transabdominal Pre-Peritoneal Repair (TAPP) For Groin Hernia In A Single Consultant Series.

Aim: TAPP repair is an established minimally invasive approach for groin hernia repair. The objective of this study was to report post-operative outcomes after TAPP repair in a single surgeon series and benchmark these against reported outcomes in the literature.

Methods: All patients who had an elective or emergency TAPP repair of a groin hernia from September 2016 to March 2020 in a district general hospital were retrospectively analysed from the electronic care record (ECR) for post-operative morbidity, re-admission, recurrence and length of hospital stay.

Lymph Node Subcapsular Sinus Microenvironment-On-A-Chip Modeling Shear Flow Relevant to Lymphatic Metastasis and Immune Cell Homing.

A lymph node sinus-on-a-chip adhesion microfluidic platform that recapitulates the hydrodynamic microenvironment of the lymph node subcapsular sinus was engineered. This device was used to interrogate the effects of lymph node remodeling on cellular adhesion in fluid flow relevant to lymphatic metastasis. Wall shear stress levels analytically estimated and modeled after quiescent and diseased/inflamed lymph nodes were experimentally recapitulated using a flow-based microfluidic perfusion system to assess the effects of physiological flow fields on human metastatic cancer cell adhesion.

Computational models of migration modes improve our understanding of metastasis.

Tumor cells migrate through changing microenvironments of diseased and healthy tissue, making their migration particularly challenging to describe. To better understand this process, computational models have been developed for both the ameboid and mesenchymal modes of cell migration. Here, we review various approaches that have been used to account for the physical environment's effect on cell migration in computational models, with a focus on their application to understanding cancer metastasis and the related phenomenon of durotaxis.

Ancestral childhood environmental exposures occurring to the grandparents and great-grandparents of the ALSPAC study children.

Cohort studies tend to be designed to look forward from the time of enrolment of the participants, but there is considerable evidence that the previous generations have a particular relevance not only in the genes that they have passed on, their cultural beliefs and attitudes, but also in the ways in which previous environmental exposures may have had non-genetic impacts, particularly for exposures during fetal life or in childhood. To investigate such non-genetic inheritance, we have collected information on the childhoods of the ancestors of the cohort of births comprising the original Avon Longitudinal Study of Parents and Children (ALSPAC). The data collected on the study child's grandparents and great grandparents comprise: (a) countries of birth; (b) years of birth; (c) age at onset of smoking; (d) whether the ancestral mothers smoked during pregnancy; (e) social class of the household; (f) information on 19 potentially traumatic situations in their childhoods such as death of a parent, being taken into care, not having enough to eat, or being in a war situation; (g) causes of death for those ancestors who had died.

KMN-159, a novel EP receptor selective agonist, stimulates osteoblastic differentiation in cultured whole rat bone marrow.

KMN-159 is the lead compound from a series of novel difluorolactam prostanoid EP receptor agonists aimed at inducing local bone formation while avoiding the inherent side effects of systemic EP activation. KMN-159 is a potent, selective small molecule possessing pharmacokinetic properties amenable to local administration. Unfractionated rat bone marrow cells (BMCs) were treated once at plating with escalating doses of KMN-159 (1 pM to 10 μM).

Photoconversion and chromatographic microfluidic system reveals differential cellular phenotypes of adhesion velocity versus persistence in shear flow.

An integrated photoconversion and cell sorting parallel-plate chromatography channel enabling the measurement of instantaneous and average velocities of cells mediating adhesion in flow fields was engineered to study the mechanisms underlying adhesion to selectins by metastatic cancer cells. Through the facile enrichment of cells into subfractions of differing adhesive behaviors and a fluorescent velocity probe amenable to off-chip analysis, underlying, causal molecular profiles implicated in differing adhesive phenotypes of metastatic cancer cells could be interrogated. This analytical method revealed selectin-mediated rolling adhesion to be strongly associated with expression of selectin ligands, correlations that vary with ligand type and rolling velocity magnitude.

Analyzing Mechanisms of Metastatic Cancer Cell Adhesive Phenotype Leveraging Preparative Adhesion Chromatography Microfluidic.

An integrated, parallel-plate microfluidic device is engineered to interrogate and fractionate cells based on their adhesivity to a substrate surface functionalized with adhesive ligand in a tightly controlled flow environment to elucidate associated cell-intrinsic pathways. Wall shear stress levels and endothelial presentation of E-selectin are modeled after the inflamed vasculature microenvironment in order to simulate in vitro conditions under which in vivo hematogenous metastasis occurs. Based on elution time from the flow channel, the collection of separate fractions of cells-noninteracting and interacting-at high yields and viabilities enables multiple postperfusion analyses, including flow cytometry, in vivo metastasis modeling, and transcriptomic analysis.

Fluorometric Quantification of Single-Cell Velocities to Investigate Cancer Metastasis.

Hematogenous metastasis is a multistep, selectin-regulated process whose mechanisms remain poorly understood. To investigate this biological pathway of cancer dissemination and better understand circulating cancer cells, we developed a high-throughput methodology that integrates organ-on-chip-like microfluidic and photoconvertible protein technologies. Our approach can ascribe single-cell velocity as a traceable cell property for off-chip analysis of the direct relationships between cell molecular profiles and adhesive phenotypes in the context of physiologically relevant fluid flow.

in Brown Rats in Grenada, West Indies.

Cat is the definitive host of the larval stage of . develops in small rodents which act as intermediate host. The aim of this study was to estimate the prevalence of in brown rats in the densely human populated parishes, St.

P-, but not E- or L-, selectin-mediated rolling adhesion persistence in hemodynamic flow diverges between metastatic and leukocytic cells.

The ability of leukocytic cells to engage selectins via rolling adhesion is critical to inflammation, but selectins are also implicated in mediating metastatic dissemination. Using a microfluidic- and flow-based cell adhesion chromatography experimental and analytical technique, we interrogated the cell-subtype differences in engagement and sustainment of rolling adhesion on P-, E-, and L-selectin-functionalized surfaces in physiological flow. Our results indicate that, particularly at low concentrations of P-selectin, metastatic but not leukocytic cells exhibit reduced rolling adhesion persistence, whereas both cell subtypes exhibited reduced persistence on L-selectin and high persistence on E-selectin, differences not revealed by flow cytometry analysis or reflected in the extent or velocity of rolling adhesion.

Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism.

Although there is considerable research into the genetic background of autism spectrum disorders, environmental factors are likely to contribute to the variation in prevalence over time. Rodent experiments indicate that environmental exposures can have effects on subsequent generations, and human studies indicate that parental prenatal exposures may play a part in developmental variation. Here we use the Avon Longitudinal Study of Parents and Children (ALSPAC) to test the hypothesis that if the mother or father (F1) had been exposed to their own mother's (F0) smoking during pregnancy, the offspring (F2) would be at increased risk of autism.

Towards a hit for every target.

Technological advances coupled with novel collaborative strategies for compound sourcing and management are poised to transform the utility of high-throughput screening.

Enrollment and response rates in a longitudinal birth cohort.

For the scientific credibility of study results, longitudinal cohort studies need to invest time, money and creative thought in establishing and maintaining the maximum number of study participants. Although success depends to a large extent on the resources available, much can be achieved by establishing a culture of integrity and enthusiasm among study staff that is conveyed to participants at all times. In this paper we outline various strategies that can be included in order to maximise the response rates.

Ethics and governance of a longitudinal birth cohort.

All longitudinal birth cohorts should be undertaken with a detailed ethical strategy and policy on governance. Here we outline the various factors that should be taken into consideration and describe ways in which these issues may be addressed.

Age no indicator of cancer survival.

Age is not a key factor in cancer survival, according to a team of researchers in Spain. And although 60 per cent of cancers occur in patients over 65, most clinical trials still exclude older people. This makes it difficult to predict how older people will respond to new cancer treatments.

Canada.

A journalist facing a life- threatening aneurism has compiled a series of essays documenting the most pressing policy implications of our ageing in societies around the worl++d as part of a public policy fellowship.

Australia.

Mental health and healthy ageing; first 24-hour care service for older Aboriginal people Older people with more sound mental health are less likely to fall according to new research from The Australian National University (ANU). The team assessed 787 adults, with an average age of 78, three times over eight years on measures of wellbeing, including depressive symptoms, morale and sense of control over their lives. The study found that there was a rising fall rate over time among those who reported an increase in depressive symptoms or reduction in morale during the course of the study.

Scientific approach to nursing recommended.

Parameters that are particularly important to the nursing care of older people feature heavily in a new report by researchers at the National Nursing Research Unit at King's College, London, which is aimed at helping nurses see the impact of the care they deliver.