Publications by authors named "Simpkin A"

Objective: To understand the impact of both frailty and chronologic age on outcomes of weaning from invasive mechanical ventilation (MV).

Methods: The study population consisted of patients enrolled in the 'WorldwidE. AssessmeNt of Separation of pAtients From ventilatory assistancE (WEAN SAFE) study.

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Background: A large body of evidence links stressful life events with depression. However, little is understood about the role of perceived impact in this association.

Methods: We performed regression analysis to investigate whether self-reported stress reactivity (derived by regressing the impact-weighted life event score on the unweighted score) moderated the association between stressful life events and depressive symptoms in adolescents from the Avon Longitudinal Study of Parents and Children cohort (n = 4791), controlling for age at outcome, sex, ethnicity, and maternal education.

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Background: Epigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk.

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Article Synopsis
  • * A new validation method identifies register errors by comparing actual residue contacts and distances in structural models to those predicted by systems like AlphaFold2, offering corrections that often improve refinement statistics.
  • * This approach is different from traditional methods as it is not reliant on stereochemistry or resolution, and it identifies potential issues in PDB entries, aiding in the accuracy of future deposits.
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The availability of highly accurate protein structure predictions from AlphaFold2 (AF2) and similar tools has hugely expanded the applicability of molecular replacement (MR) for crystal structure solution. Many structures can be solved routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD).

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This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the relative effectiveness and vascular access device (VAD)-related complications of VADs in people requiring prolonged systemic anti-cancer treatment.

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Importance: Epigenetic age acceleration is associated with exposure to social and economic adversity and may increase the risk of premature morbidity and mortality. However, no studies have included measures of structural racism, and few have compared estimates within or across the first and second generation of epigenetic clocks.

Objective: To determine whether epigenetic age acceleration is positively associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods.

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Background: Epigenetic Age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk.

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Peripheral intravenous cannulation and venipuncture are among the most common invasive procedures in health care and are not without risks or complications. The aim of this study was to evaluate the current training provided to nursing and midwifery undergraduate students. Student knowledge, attitude, practice, and performance regarding these procedural skills were assessed.

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  • - The study investigates the Intra-Discal Vacuum Phenomenon (IDVP) in lumbar spines of people over 60, finding that IDVP is common, affecting over 50% of the sample, and its severity increases towards the lower spine.
  • - Using CT scans, researchers analyzed 2020 cases to understand how age, pelvic incidence (PI), and degenerative issues like fractures impact the occurrence of IDVP.
  • - Results suggest that lower pelvic incidence correlates with higher IDVP rates, especially at the L5S1 level, and reveal connections between IDVP and other spinal degenerative conditions, contributing to the understanding of aging spine mechanics.
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  • The study involved analyzing CT scans of the lumbar spine in older adults to understand the relationship between intradiscal vacuum phenomenon (IDVP) and disc degeneration over time.
  • Results showed that while most cases of IDVP stayed at a similar severity, some worsened, improved, or fused, with new cases developing in some patients during the study period.
  • Interestingly, the presence of IDVP did not correlate with significantly worse back pain among participants, suggesting that back pain experiences vary despite degeneration severity.
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  • The COVID-19 pandemic led to significant treatment delays for patients needing transcatheter aortic valve replacement (TAVR), with a marked decrease in procedure volumes during the first two waves of the pandemic.
  • The study analyzed TAVR case data from 130 centers in 61 countries, finding a 15% drop in cases during the first wave and 7% in the second, particularly affecting regions like Africa, Central-South America, and Asia.
  • Factors such as hospital type (private vs public), urban vs rural location, low procedure volumes, a country's socioeconomic status, and stringent public health measures contributed to these reductions, highlighting the need for improved public health policies for future health crises.
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Importance: Epigenetic accelerated aging is associated with exposure to social and economic adversity and may increase risk of premature morbidity and mortality. However, no studies have included measures of structural racism and few have compared estimates within or across the 1 and 2 generation of epigenetic clocks (the latter additionally trained on phenotypic data).

Objective: To determine if accelerated epigenetic aging is associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods.

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Background: Independent testing of home blood pressure (BP) measurement (HBPM) devices is often lacking, particularly among older and multi-morbid patients.

Methods: We studied the Bpro G2 (using tonometry), Omron HeartGuide (using occlusive oscillometric technology), and Heartisans (using photoplethysmography) wrist watch HBPM devices against a gold standard brachial sphygmomanometer. To test device performance, we used the ISO81060-2 protocol (though this protocol cannot formally validate cuffless devices).

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Importance: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination.

Objective: Our study tests the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied.

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The prediction of RNA three-dimensional structures remains an unsolved problem. Here, we report assessments of RNA structure predictions in CASP15, the first CASP exercise that involved RNA structure modeling. Forty-two predictor groups submitted models for at least one of twelve RNA-containing targets.

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The results of tertiary structure assessment at CASP15 are reported. For the first time, recognizing the outstanding performance of AlphaFold 2 (AF2) at CASP14, all single-chain predictions were assessed together, irrespective of whether a template was available. At CASP15, there was no single stand-out group, with most of the best-scoring groups-led by PEZYFoldings, UM-TBM, and Yang Server-employing AF2 in one way or another.

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Background: Angiography-derived computational physiology is an appealing alternative to pressure-wire coronary physiology assessment. However, little is known about its reliability in the setting of severe aortic stenosis. This study sought to provide an integrated assessment of epicardial and microvascular coronary circulation by means of single-view angiography-derived physiology in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).

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Purpose: Cytoreductive surgery (CRS) is often combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal tumour deposits. Considering CRS, the evidence relating the large incisions, local chemotherapy and abdominal wall trauma to incisional hernias (IH) has not been synthesized. This systematic review and meta-analysis was conducted to examine the proportion of IH present in patients post CRS and the effect HIPEC had on these rates.

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Background: Time-sensitive emergencies in areas of low population density have statistically poorer outcomes. This includes incidents of major trauma. This study assesses the effect that population density at a receiving hospital of a major trauma patient has on survival.

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The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its effects via soft robotic actuations.

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In late 2020, the results of CASP14, the 14th event in a series of competitions to assess the latest developments in computational protein structure-prediction methodology, revealed the giant leap forward that had been made by Google's Deepmind in tackling the prediction problem. The level of accuracy in their predictions was the first instance of a competitor achieving a global distance test score of better than 90 across all categories of difficulty. This achievement represents both a challenge and an opportunity for the field of experimental structural biology.

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Article Synopsis
  • Epigenetic clocks help scientists understand how different factors affect healthy aging, including social conditions, but there isn’t enough focus on who the participants in studies are.
  • The characteristics of participants, like age, gender, and race, are important since they can influence results and health outcomes.
  • Many studies don’t report this information well, making it hard for other researchers to know if the models they create will work for different kinds of people.
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  • - Recent advancements in computational structural biology are enhancing our understanding of clinically important proteins, with a focus on human Oca2, which is linked to a common form of albinism.
  • - Oca2's structure, modeled using techniques like AlphaFold2, reveals it has a unique scaffold and transport domain, along with a previously unidentified cryptic GOLD domain that aids in protein trafficking.
  • - Analysis indicates that Oca2 could function as a Na+/dicarboxylate symporter, with significant mutations mapping to its structural features, and models suggest it may operate via an elevator-type transport mechanism.
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  • Childhood adversity affects DNA methylation patterns, potentially changing health outcomes throughout development, particularly during sensitive periods.
  • The study looked at data from the Avon Longitudinal Study of Parents and Children, focusing on various types of childhood adversity and its impact on DNA methylation at age 15.
  • Using structured life course modeling, researchers evaluated how timing, accumulation, and recency of adversity influence adolescent DNA methylation and aimed to replicate findings with other studies.
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