A Pharmacogenomic and Protein Analysis of Human Lacrimal Fluid in Varying Age Groups

Proteins are large biological molecules located within all cells. They are considered the basic functional components of cells that allow them to operate appropriately. Genes consist of both DNA and RNA, and are the cellular components that code for the proteins. A biomarker is any cellular component that is an indication of a biological state. Therefore, genetic and protein biomarkers are specific genes and proteins, respectively, present in cells that indicate a specific biological state of a cell. Identification of proteins and genetic biomarkers in relative quantities has been found to reflect various disease states and age groups in humans. Comparisons of possible techniques for collecting lacrimal fluids from human subjects which could potentially be utilized in the design of the study

Diagnostic Utility of the Impact of Event Scale-Revised in Two Samples of Survivors of War

The study aimed at examining the diagnostic utility of the Impact of Event Scale-Revised (IES-R) as a screening tool for post-traumatic stress disorder (PTSD) in survivors of war. The IES-R was completed by two independent samples that had survived the war in the Balkans: a sample of randomly selected people who had stayed in the area of former conflict (n = 3,313) and a sample of refugees to Western European countries (n = 854). PTSD was diagnosed using the MINI International Neuropsychiatric Interview. Prevalence of PTSD was 20.1% in the Balkan sample and 33.1% in the refugee sample. Results revealed that when considering a minimum value of specificity of 0.80, the optimally sensitive cut-off score for screening for PTSD in the Balkan sample was 34. In both the Balkan sample and the refugee sample, this cut-off score provided good values on sensitivity (0.86 and 0.89, respectively) and overall efficiency (0.81 and 0.79, respectively). Further, the kappa coefficients for sensitivity for the cut-off of 34 were 0.80 in both samples. Findings of this study support the clinical utility of the IES-R as a screening tool for PTSD in large-scale research studies and intervention studies if structured diagnostic interviews are regarded as too labor-intensive and too costly

Yoda1 and phosphatidylserine exposure in red cells from patients with sickle cell anaemia

Abstract: Phosphatidylserine (PS) exposure is increased in red cells from sickle cell anaemia (SCA) patients. Externalised PS is prothrombotic and attractive to phagocytes and activated endothelial cells and thus contributes to the anaemic and ischaemic complications of SCA. The mechanism of PS exposure remains uncertain but it can follow increased intracellular Ca2+ concentration ([Ca2+]i). Normally, [Ca2+]i is maintained at very low levels but in sickle cells, Ca2+ permeability is increased, especially following deoxygenation and sickling, mediated by a pathway sometimes called Psickle. The molecular identity of Psickle is also unclear but recent work has implicated the mechanosensitive channel, PIEZO1. We used Yoda1, an PIEZO1 agonist, to investigate its role in sickle cells. Yoda1 caused an increase in [Ca2+]i and PS exposure, which was inhibited by its antagonist Dooku1 and the PIEZO1 inhibitor GsMTx4, consistent with functional PIEZO1. However, PS exposure did not necessitate an increase in [Ca2+]i. Two PKC inhibitors were also tested, chelerytherine chloride and calphostin C. Both reduced PS exposure whilst chelerytherine chloride also reduced Yoda1-induced increases in [Ca2+]i. Findings are therefore consistent with the presence of PIEZO1 in sickle cells, able to mediate Ca2+ entry but that PKC was also involved in both Ca2+ entry and PS exposure

Synoptic relationships between surface Chlorophyll-<i>a</i> and diagnostic pigments specific to phytoplankton functional types

Error-quantified, synoptic-scale relationships between chlorophyll-<i>a</i> (Chl-<i>a</i>) and phytoplankton pigment groups at the sea surface are presented. A total of ten pigment groups were considered to represent three Phytoplankton Size Classes (PSCs, micro-, nano- and picoplankton) and seven Phytoplankton Functional Types (PFTs, i.e. diatoms, dinoflagellates, green algae, prymnesiophytes (haptophytes), pico-eukaryotes, prokaryotes and <i>Prochlorococcus</i> sp.). The observed relationships between Chl-<i>a</i> and PSCs/PFTs were well-defined at the global scale to show that a community shift of phytoplankton at the basin and global scales is reflected by a change in Chl-<i>a</i> of the total community. Thus, Chl-<i>a</i> of the total community can be used as an index of not only phytoplankton biomass but also of their community structure. Within these relationships, we also found non-monotonic variations with Chl-<i>a</i> for certain pico-sized phytoplankton (pico-eukaryotes, Prokaryotes and <i>Prochlorococcus</i> sp.) and nano-sized phytoplankton (Green algae, prymnesiophytes). The relationships were quantified with a least-square fitting approach in order to enable an estimation of the PFTs from Chl-<i>a</i> where PFTs are expressed as a percentage of the total Chl-<i>a</i>. The estimated uncertainty of the relationships depends on both PFT and Chl-<i>a</i> concentration. Maximum uncertainty of 31.8% was found for diatoms at Chl-<i>a</i> = 0.49 mg m⁻³. However, the mean uncertainty of the relationships over all PFTs was 5.9% over the entire Chl-<i>a</i> range observed in situ (0.02 &lt; Chl-<i>a</i> &lt; 4.26 mg m^&minus;3). The relationships were applied to SeaWiFS satellite Chl-<i>a</i> data from 1998 to 2009 to show the global climatological fields of the surface distribution of PFTs. Results show that microplankton are present in the mid and high latitudes, constituting only ~10.9% of the entire phytoplankton community in the mean field for 1998–2009, in which diatoms explain ~7.5%. Nanoplankton are ubiquitous throughout the global surface oceans, except the subtropical gyres, constituting ~45.5%, of which prymnesiophytes (haptophytes) are the major group explaining ~31.7% while green algae contribute ~13.9%. Picoplankton are dominant in the subtropical gyres, but constitute ~43.6% globally, of which prokaryotes are the major group explaining ~26.5% (<i>Prochlorococcus</i> sp. explaining 22.8%), while pico-eukaryotes explain ~17.2% and are relatively abundant in the South Pacific. These results may be of use to evaluate global marine ecosystem models

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study

BACKGROUND: Around 60,000 babies are born preterm (prior to 37 weeks' gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). OBJECTIVE: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 'Mode of delivery for preterm infants'). METHODS: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). RESULTS: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26-32 weeks' gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. CONCLUSION: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. FUTURE WORK: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. LIMITATIONS: Certainty that a trial could be conducted can be determined only when it is attempted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12295730. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information

Model validation for a noninvasive arterial stenosis detection problem

Copyright @ 2013 American Institute of Mathematical SciencesA current thrust in medical research is the development of a non-invasive method for detection, localization, and characterization of an arterial stenosis (a blockage or partial blockage in an artery). A method has been proposed to detect shear waves in the chest cavity which have been generated by disturbances in the blood flow resulting from a stenosis. In order to develop this methodology further, we use both one-dimensional pressure and shear wave experimental data from novel acoustic phantoms to validate corresponding viscoelastic mathematical models, which were developed in a concept paper [8] and refined herein. We estimate model parameters which give a good fit (in a sense to be precisely defined) to the experimental data, and use asymptotic error theory to provide confidence intervals for parameter estimates. Finally, since a robust error model is necessary for accurate parameter estimates and confidence analysis, we include a comparison of absolute and relative models for measurement error.The National Institute of Allergy and Infectious Diseases, the Air Force Office of Scientific Research, the Deopartment of Education and the Engineering and Physical Sciences Research Council (EPSRC)

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required

Assessment of a regional physical-biogeochemical stochastic ocean model. Part 2: Empirical consistency

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordIn this Part 2 article of a two-part series, observations based on satellite missions were used to evaluate the empirical consistency of model ensembles generated via stochastic modelling of ocean physics and biogeochemistry. A high-resolution Bay of Biscay configuration was used as a case study to explore the model error subspace in both the open and coastal ocean. In Part 1 of this work, three experiments were carried out to generate model ensembles by perturbing only physics, only biogeochemistry, and both of them simultaneously. In Part 2 of this work, empirical consistency was checked, first by means of rank histograms projecting the data onto the model ensemble classes, and second, by pattern-selective consistency criteria in the space of “array modes” defined as eigenvectors of the representer matrix. Rank histograms showed large dependency on geographical region and on season for sea surface temperature (SST), sea-level anomaly (SLA), and phytoplankton functional types (PFT), shifting from consistent model-data configurations to large biases because of model ensemble underspread. Consistency for SST array modes was found to be verified at large, small and coastal scales soon after the ensemble spin-up. Array modes for the along-track sea-level showed useful consistent information at large scales and at the mesoscale; for the gridded SLA was verified only at large scale. Array modes showed that biogeochemical model uncertainties generated by stochastic physics, were effectively detected by PFT measurements at large scales, as well as at mesoscale and small-scale. By contrast, perturbing only biogeochemistry, with an identical physical forcing across the ensemble, limits the potential of PFT measurements at detecting and possibly correcting small-scale biogeochemical model errors. When an ensemble was found to be inconsistent with observations along a particular direction (here, an array mode), a plausible reason is that other error processes must have been active in the model, in addition to the ones at work across the ensemble.Centre National de la Recherche Scientifique (CNRS)European Unio