Longitudinal Data with Follow-up Truncated by Death: Match the Analysis Method to Research Aims

Diverse analysis approaches have been proposed to distinguish data missing due to death from nonresponse, and to summarize trajectories of longitudinal data truncated by death. We demonstrate how these analysis approaches arise from factorizations of the distribution of longitudinal data and survival information. Models are illustrated using cognitive functioning data for older adults. For unconditional models, deaths do not occur, deaths are independent of the longitudinal response, or the unconditional longitudinal response is averaged over the survival distribution. Unconditional mod- els, such as random effects models fit to unbalanced data, may implicitly impute data beyond the time of death. Fully conditional models stratify the longitudinal response trajectory by time of death. Fully conditional models are effective for describing in- dividual trajectories, in terms of either aging (age, or years from baseline) or dying (years from death). Causal models (principal stratification) as currently applied are fully conditional models, since group differences at one timepoint are described for a cohort that will survive past a later timepoint. Partly conditional models summarize the longitudinal response in the dynamic cohort of survivors. Partly conditional models are serial cross-sectional snapshots of the response, reflecting the average response in survivors at a given timepoint rather than individual trajectories. Joint models of sur- vival and longitudinal response describe the evolving health status of the entire cohort. Researchers using longitudinal data should consider which method of accommodating deaths is consistent with research aims, and use analysis methods accordingly

Abdominal Wound Problems After Hysterectomy With Electrocautery vs. Scalpel Subcutaneous Incision

The purpose of this study was to evaluate the relationship between postoperative abdominal incision problems and opening subcutaneous tissues with electrocautery or scalpel. Women scheduled for elective abdominal hysterectomy who gave informed consent were randomly assigned to subcutaneous abdominal wall tissue incision by electrocautery or scalpel. Postoperative abdominal wound problem diagnoses included seroma, hematoma, infection, or dehiscence without identifiable etiology. Fifteen of 380 women (3.9%) developed a wound problem; six had scalpel and nine had electrosurgical subcutaneous incisions (P = 0.4). Thicker subcutaneous tissues (P = 0.04) and concurrent pelvic infection (P < 0.001) were significant risk factors for postoperative wound problems. Only two women (0.5%) developed an infection. We conclude that the method of subcutaneous tissue incision was unrelated to the development of postoperative abdominal incision problems in 380 women undergoing elective abdominal hysterectomy

Oligodeoxynucleotides ODN 2006 and M362 Exert Potent Adjuvant Effect through TLR-9/-6 Synergy to Exaggerate Mammaglobin-A Peptide Specific Cytotoxic CD8+T Lymphocyte Responses against Breast Cancer Cells

Mammaglobin-A (MamA) is overexpressed in 40–80% of all human breast cancers. Recent phase I clinical trials of the MamA DNA vaccine showed encouraging safety outcomes. However, this vaccine elicited only a modest increase in MamA specific CD8+T lymphocyte (CTL) activation. As vaccine adjuvants play a critical role in enhancing the immunotherapeutic efficiency of vaccines, we tested the potential role of three synthetic CpG oligodeoxynucleotides (ODN2216—class A ODN, ODN2006—class B ODN, and ODN M362—class C ODN) to further enhance MamA specific CTL responses. Towards this, naïve CD8+T cells were obtained from healthy HLA-A2+ human donors. The HLA-A2 specific immunodominant epitope of MamA, MamA2.1 (LIYDSSLCDL), was utilized to activate naïve CD8+T cells. The THP-1 (HLA-A2+) cells were used as antigen presenting cells to stimulate naïve CD8+T cells along with (or without) co-treatment of various ODNs mentioned above. Activation of naïve CD8+T cells with the MamA2.1 peptide along with ODNs demonstrated enhanced MamA specific CTL mediated cytotoxicity on AU565 (HLA-A+/MamA+) breast cancer cells following co-treatment with ODN2006 and M362 compared to ODN2216 or MamA2.1 peptide alone. However, no significant cytotoxicity was noted upon treatment of MamA2.1 activated CTLs on MCF7 (HLA-A+/MamA−) cells, suggesting that the activation of CTLs is specific to the MamA antigen. Functional characterization studies demonstrated specific IL-12 mediated cross-talk between TLR-6 and -9 in THP-1 cells following stimulation with ODN2006 and M362, which was critical for the final cytotoxic activation of CD8+T lymphocytes. Based on these data, we conclude that ODN2006 and ODN M362 exerted a strong adjuvant effect through induction of the initial innate immune response through TLR9 upregulation followed by enhanced MamA specific CTL dependent adaptive immune responses. Our current data provide evidence for the application of Class-B/-C-CpG-ODNs as potential vaccine adjuvants towards enhancing the success of MamA based breast cancer vaccination

Prophylactic Antibiotics for Suction Curettage in Incomplete Abortion

Objective: The purpose of this study was to investigate the efficacy of 200 mg of prophylactic doxycycline in preventing pelvic infection after curettage for spontaneous (incomplete) abortion

Primary palliative care research: opportunities and challenges.

INTRODUCTION: Primary care has a central role in palliative and end of life care: 45.6% of deaths in England and Wales occur under the care of primary care teams at home or in care homes. The Community Care Pathways at the End of Life (CAPE) study investigated primary care provided for patients in the final 6 months of life. This paper highlights the opportunities and challenges associated with primary palliative care research in the UK, describing the methodological, ethical, logistical and gatekeeping challenges encountered in the CAPE study and how these were addressed. THE STUDY METHODS: Using a mixed-methods approach, quantitative data were extracted from the general practitioner (GP) and district nurse (DN) records of 400 recently deceased patients in 20 GP practices in the East of England. Focus groups were conducted with some GPs and DNs, and individual interviews held with bereaved carers and other GPs and DNs. THE CHALLENGES ADDRESSED: Considerable difficulties were encountered with ethical permissions, with GP, DN and bereaved carer recruitment and both quantitative and qualitative data collection. These were overcome with flexibility of approach, perseverance of the research team and strong user group support. This enabled completion of the study which generated a unique primary palliative care data set.National Institute for Health Research (NIHR) Research for Patient Benefit Programme. National Institute for Health Research (NIHR) School for Primary Care Research (SPCR). National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of Englan

The role of pre-school quality in promoting resilience in the cognitive development of young children

The study reported here investigates the role of pre-school education as a protective factor in the development of children who are at risk due to environmental and individual factors. This investigation builds upon earlier research by examining different kinds of 'quality' in early education and tests the hypothesis that pre-schools of high quality can moderate the impacts of risks upon cognitive development. Cognitive development was measured in 2857 English pre-schoolers at 36 and 58 months of age, together with 22 individual risks to children's development, and assessments were made of the quality of their pre-school provision. Multilevel Structural Equation Modelling revealed that: the global quality of pre-school can moderate the effects of familial risk (such as poverty); the relationships between staff and children can moderate the effects of child level risk (such as low birth weight); and the specific quality of curricular provision can moderate the effects of both. Policy makers need to take quality into account in their efforts to promote resilience in young 'at risk' children through early childhood services

RELICS: Strong Lens Models for Five Galaxy Clusters From the Reionization Lensing Cluster Survey

Strong gravitational lensing by galaxy clusters magnifies background galaxies, enhancing our ability to discover statistically significant samples of galaxies at z>6, in order to constrain the high-redshift galaxy luminosity functions. Here, we present the first five lens models out of the Reionization Lensing Cluster Survey (RELICS) Hubble Treasury Program, based on new HST WFC3/IR and ACS imaging of the clusters RXC J0142.9+4438, Abell 2537, Abell 2163, RXC J2211.7-0349, and ACT-CLJ0102-49151. The derived lensing magnification is essential for estimating the intrinsic properties of high-redshift galaxy candidates, and properly accounting for the survey volume. We report on new spectroscopic redshifts of multiply imaged lensed galaxies behind these clusters, which are used as constraints, and detail our strategy to reduce systematic uncertainties due to lack of spectroscopic information. In addition, we quantify the uncertainty on the lensing magnification due to statistical and systematic errors related to the lens modeling process, and find that in all but one cluster, the magnification is constrained to better than 20% in at least 80% of the field of view, including statistical and systematic uncertainties. The five clusters presented in this paper span the range of masses and redshifts of the clusters in the RELICS program. We find that they exhibit similar strong lensing efficiencies to the clusters targeted by the Hubble Frontier Fields within the WFC3/IR field of view. Outputs of the lens models are made available to the community through the Mikulski Archive for Space TelescopesComment: Accepted to Ap

Species-level view of population structure and gene flow for a critically endangered primate (Varecia variegata)

Lemurs are among the world\u27s most threatened mammals. The critically endangered black-and-white ruffed lemur (Varecia variegata), in particular, has recently experienced rapid population declines due to habitat loss, ecological sensitivities to habitat degradation, and extensive human hunting pressure. Despite this, a recent study indicates that ruffed lemurs retain among the highest levels of genetic diversity for primates. Identifying how this diversity is apportioned and whether gene flow is maintained among remnant populations will help to diagnose and target conservation priorities. We sampled 209 individuals from 19 sites throughout the remaining V. variegata range. We used 10 polymorphic microsatellite loci and ∼550 bp of mtDNA sequence data to evaluate genetic structure and population dynamics, including dispersal patterns and recent population declines. Bayesian cluster analyses identified two distinct genetic clusters, which optimally partitioned data into populations occurring on either side of the Mangoro River. Localities north of the Mangoro were characterized by greater genetic diversity, greater gene flow (lower genetic differentiation) and higher mtDNA haplotype and nucleotide diversity than those in the south. Despite this, genetic differentiation across all sites was high, as indicated by high average FST (0.247) and ΦST (0.544), and followed a pattern of isolation-by-distance. We use these results to suggest future conservation strategies that include an effort to maintain genetic diversity in the north and restore connectivity in the south. We also note the discordance between patterns of genetic differentiation and current subspecies taxonomy, and encourage a re-evaluation of conservation management units moving forward

Sea Ice and Substratum Shape Extensive Kelp Forests in the Canadian Arctic

The coastal zone of the Canadian Arctic represents 10% of the world’s coastline and is one of the most rapidly changing marine regions on the planet. To predict the consequences of these environmental changes, a better understanding of how environmental gradients shape coastal habitat structure in this area is required. We quantified the abundance and diversity of canopy forming seaweeds throughout the nearshore zone (5–15 m) of the Eastern Canadian Arctic using diving surveys and benthic collections at 55 sites distributed over 3,000 km of coastline. Kelp forests were found throughout, covering on average 40.4% (±29.9 SD) of the seafloor across all sites and depths, despite thick sea ice and scarce hard substrata in some areas. Total standing macroalgal biomass ranged from 0 to 32 kg m–2 wet weight and averaged 3.7 kg m–2 (±0.6 SD) across all sites and depths. Kelps were less abundant at depths of 5 m compared to 10 or 15 m and distinct regional assemblages were related to sea ice cover, substratum type, and nutrient availability. The most common community configuration was a mixed assemblage of four species: Agarum clathratum (14.9% benthic cover ± 12.0 SD), Saccharina latissima (13% ± 14.7 SD), Alaria esculenta (5.4% ± 1.2 SD), and Laminaria solidungula (3.7% ± 4.9 SD). A. clathratum dominated northernmost regions and S. latissima and L. solidungula occurred at high abundance in regions with more open water days. In southeastern areas along the coast of northern Labrador, the coastal zone was mainly sea urchin barrens, with little vegetation. We found positive relationships between open water days (days without sea ice) and kelp biomass and seaweed diversity, suggesting kelp biomass could increase, and the species composition of kelp forests could shift, as sea ice diminishes in some areas of the Eastern Canadian Arctic. Our findings demonstrate the high potential productivity of this extensive coastal zone and highlight the need to better understand the ecology of this system and the services it provides.publishedVersio