A targeted approach to vaccine hesitancy

This short communication makes the case for targeted vaccine research when attempting to counter hesitancy, especially amongst vulnerable or rarefied patient groups. Far from disincentivizing vaccination, the freedom to research and publicize the limitations of these technologies for certain groups and personalizing dosing, pacing, adjuvants, and time-sensitive alternatives in response is essential for optimizing health outcomes while neutralizing the vaccine research landscape itself. Vaccine evangelism only arouses suspicion when it is not tempered by rigorous research into differential vaccine benefit-risk in this way. That said, the long-standing politicization of vaccination—a topic vulnerable to misinterpretation and media sensationalism—along with the commercial incentives associated with universal adoption makes more comparative and critical research difficult to fund and promote in practice. Likewise, a prescriptive approach to vaccination does little to address the issues of vaccine inequality that contribute to both hesitancy and conspiracy globally and will likely prove financially prohibitive in certain markets. These obstacles are not insurmountable, however, provided that comparative research is centrally subsidized, regulations ensure that vaccine development trials explore differentiated outcomes, especially amongst high-risk or rare groups, and findings are used to prioritize global vaccine allocation to those that stand to benefit most from them

Pass the tissue: restoring researcher access to legal human donations

The sensitivity of human tissue and previous instances of misuse have, rightfully, led to the introduction of far-reaching oversight and regulatory mechanisms for accessing, storing and sharing samples. However, these restrictions, in tandem with more broad-based privacy regulations, have had the unintended consequence of obstructing legitimate requests for medical materials. This is of real detriment to ambitions for biomedical research, most notably the precision medicine agenda. As such, this paper makes the case for facilitating authorised researcher access to human tissue and associated data along practical medical ethics lines, detailing how liberating samples from unfit regulations, re-evaluating biobanks, diversifying considerations for donor benefit-risk, future proofing donor consent and flattening hierarchies of donation acceptability equate to a more cohesive and respectful means of managing biological samples and information than is achieved at present

Studies of Diffuse Interstellar Bands. V. Pairwise Correlations of Eight Strong DIBs and Neutral Hydrogen, Molecular Hydrogen, and Color Excess

We establish correlations between equivalent widths of eight diffuse interstellar bands (DIBs), and examine their correlations with atomic hydrogen, molecular hydrogen, and EB-V . The DIBs are centered at \lambda\lambda 5780.5, 6204.5, 6283.8, 6196.0, 6613.6, 5705.1, 5797.1, and 5487.7, in decreasing order of Pearson\^as correlation coefficient with N(H) (here defined as the column density of neutral hydrogen), ranging from 0.96 to 0.82. We find the equivalent width of \lambda 5780.5 is better correlated with column densities of H than with E(B-V) or H2, confirming earlier results based on smaller datasets. We show the same is true for six of the seven other DIBs presented here. Despite this similarity, the eight strong DIBs chosen are not well enough correlated with each other to suggest they come from the same carrier. We further conclude that these eight DIBs are more likely to be associated with H than with H2, and hence are not preferentially located in the densest, most UV shielded parts of interstellar clouds. We suggest they arise from different molecules found in diffuse H regions with very little H (molecular fraction f<0.01). Of the 133 stars with available data in our study, there are three with significantly weaker \lambda 5780.5 than our mean H-5780.5 relationship, all of which are in regions of high radiation fields, as previously noted by Herbig. The correlations will be useful in deriving interstellar parameters when direct methods are not available. For instance, with care, the value of N(H) can be derived from W{\lambda}(5780.5).Comment: Accepted for publication in The Astrophysical Journal; 37 pages, 11 figures, 6 table

Disparities in COVID-19 mortality amongst the immunosuppressed: a systematic review and meta-analysis for enhanced disease surveillance

Background: Effective disease surveillance, including that for COVID-19, is compromised without a standardised method for categorising the immunosuppressed as a clinical risk group. Methods: We conducted a systematic review and meta-analysis to evaluate whether excess COVID-associated mortality compared to the immunocompetent could meaningfully subdivide the immunosuppressed. Our study adhered to UK Immunisation against infectious disease (Green Book) criteria for defining and categorising immunosuppression. Using OVID (EMBASE, MEDLINE, Transplant Library, and Global Health), PubMed, and Google Scholar, we examined relevant literature between the entirety of 2020 and 2022. We selected for cohort studies that provided mortality data for immunosuppressed subgroups and immunocompetent controls. Meta-analyses, grey literature and any original works that failed to provide comparator data or reported all-cause or paediatric outcomes were excluded. Odds Ratios (OR) and 95% confidence intervals (CI) of COVID-19 mortality were meta-analysed by immunosuppressed category and subcategory. Subgroup analyses differentiated estimates by effect measure, country income, study setting, level of adjustment, use of matching and publication year. Study screening, extraction and bias assessment were performed blinded and independently by two researchers; conflicts were resolved with the oversight of a third researcher. PROSPERO registration number is CRD42022360755. Findings: We identified 99 unique studies, incorporating data from 1,542,097 and 56,248,181 unique immunosuppressed and immunocompetent patients with COVID-19 infection, respectively. Compared to immunocompetent people (pooled OR, 95%CI), solid organ transplants (2.12, 1.50-2.99) and malignancy (2.02, 1.69-2.42) patients had a very high risk of COVID-19 mortality. Patients with rheumatological conditions (1.28, 1.13-1.45) and HIV (1.20, 1.05-1.36) had just slightly higher risks than the immunocompetent baseline. Case type, setting income and mortality data matching and adjustment were significant modifiers of excess immunosuppressed mortality for some immunosuppressed subgroups. Interpretation: Excess COVID-associated mortality among the immunosuppressed compared to immunocompetent was seen to vary significantly across subgroups. This novel means of subdivision has prospective benefit for targeting patient triage, shielding and vaccination policies during periods of high disease transmission. Funding: Supported by EMIS Health and the UK Medical Research Council. Grant number: MR/R015708/1

Estimated health economic impact of conducting urine albumin-to-creatinine ratio testing alongside estimated glomerular filtration rate testing in the early stages of chronic kidney disease in patients with type 2 diabetes

Aim: To estimate the health economic impact of undertaking urine albumin-to-creatinine ratio (UACR) testing versus no UACR testing in early stages of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). Methods: An economic model, taking a UK healthcare system perspective, estimated the impact of UACR testing on additional costs, clinical benefits measured as prevented dialyses and cardiovascular-related deaths, life years gained (LYg), LYg before kidney failure, and incremental cost-effectiveness ratio (ICER). Sixteen of the 18 Kidney Disease: Improving Global Outcomes (KDIGO) heatmap categories were considered separately, and grouped in health states according to CKD risk. Results were derived for current standard-of-care and emerging CKD therapies. Results: The cohort that adhered to both UACR and estimated glomerular filtration rate (eGFR) testing guidelines in early stages of CKD (n = 1000) was associated with approximately 500 LYg before kidney failure onset; costing approximately £2.5 M. ICERs across the KDIGO heatmap categories were approximately £5,000. Limitations: This model used data from a comprehensive meta-analysis that was initiated more than 10 years ago (2009). While this was the most comprehensive source identified, recent changes in the treatment landscape, patient population and social determinants of CKD will not be captured. Furthermore, a narrow approach was taken, aligning included costs with UK NHS reference materials. This means that some direct and indirect drivers of costs in late-stage disease have been excluded. Conclusions: UACR testing in the early stages of CKD is cost effective in T2D patients. Emerging therapies with the potential to slow CKD progression, mean that optimal monitoring through UACR/eGFR testing will become increasingly important for accurate identification and timely treatment initiation, particularly for the highest-risk A3 category

Parasitic Infection Surveillance in Mississippi Delta Children

Some recent studies suggest ongoing transmission of parasitic diseases in the American South; however, surveys in Mississippi children are lacking. We enrolled 166 children (median age 8 years, range 4–13 years) from the Mississippi Delta region and carried out multi-parallel real-time polymerase chain reaction (PCR) for Necator americanus, Ascaris lumbricoides, and Strongyloides stercoralis on their stool samples. Dried blood spots were obtained for multiplex serology antibody detection. Of 166 children, all reported having flushable toilets, 11% had soil exposure, and 34% had a pet dog or cat. None had prior diagnosis or treatment of parasitic disease. Multi-parallel real-time PCRs were negative on the 89 stool DNA extracts available for testing. Dried blood spot testing of all 166 children determined the seroprevalence of IgG antibodies to Toxocara spp. (3.6%), Cryptosporidium (2.4%), S. stercoralis, Fasciola hepatica, and Giardia duodenalis (all 0%). In conclusion, parasitic infections and exposure were scarce in this population. Larger studies of at-risk populations are needed

Parasitic Disease Surveillance, Mississippi, USA

Surveillance for soil-transmitted helminths, strongyloidiasis, cryptosporidiosis, and giardiasis was conducted in Mississippi, USA. PCR performed on 224 fecal samples for all soil-transmitted helminths and on 370 samples for only Necator americanus and Strongyloides stercoralis identified 1 S. stercoralis infection. Seroprevalences were 8.8% for Toxocara, 27.4% for Cryptosporidium, 5.7% for Giardia, and 0.2% for Strongyloides parasites

Measurement of Bottom versus Charm as a Function of Transverse Momentum with Electron-Hadron Correlations in p+p Collisions at sqrt(s)=200 GeV

The momentum distribution of electrons from semi-leptonic decays of charm and bottom for mid-rapidity |y|<0.35 in p+p collisions at sqrt(s)=200 GeV is measured by the PHENIX experiment at the Relativistic Heavy Ion Collider (RHIC) over the transverse momentum range 2 < p_T < 7 GeV/c. The ratio of the yield of electrons from bottom to that from charm is presented. The ratio is determined using partial D/D^bar --> e^{+/-} K^{-/+} X (K unidentified) reconstruction. It is found that the yield of electrons from bottom becomes significant above 4 GeV/c in p_T. A fixed-order-plus-next-to-leading-log (FONLL) perturbative quantum chromodynamics (pQCD) calculation agrees with the data within the theoretical and experimental uncertainties. The extracted total bottom production cross section at this energy is \sigma_{b\b^bar}= 3.2 ^{+1.2}_{-1.1}(stat) ^{+1.4}_{-1.3}(syst) micro b.Comment: 432 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Identified charged hadron production in p+p collisions at sqrt(s)=200 and 62.4 GeV

Transverse momentum distributions and yields for $\pi^{\pm}$, $K^{\pm}$, $p$ and $\bar{p}$ in $p+p$ collisions at $\sqrt{s}$=200 and 62.4 GeV at midrapidity are measured by the PHENIX experiment at the Relativistic Heavy Ion Collider (RHIC). These data provide important baseline spectra for comparisons with identified particle spectra in heavy ion collisions at RHIC. We present the inverse slope parameter $T_{\rm inv}$, mean transverse momentum $$ and yield per unit rapidity $dN/dy$ at each energy, and compare them to other measurements at different $\sqrt{s}$ in $p+p$ and $p+\bar{p}$ collisions. We also present the scaling properties such as $m_T$ scaling, $x_T$ scaling on the $p_T$ spectra between different energies. To discuss the mechanism of the particle production in $p+p$ collisions, the measured spectra are compared to next-to-leading-order or next-to-leading-logarithmic perturbative quantum chromodynamics calculations.Comment: 431 authors from 62 institutions, 32 pages, 23 figures, and 18 tables. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross section and double helicity asymmetry for eta mesons and their comparison to neutral pion production in p+p collisions at sqrt(s)=200 GeV

Measurements of double-helicity asymmetries for inclusive hadron production in polarized p+p collisions are sensitive to helicity--dependent parton distribution functions, in particular to the gluon helicity distribution, Delta(g). This study focuses on the extraction of the double-helicity asymmetry in eta production: polarized p+p --> eta + X, the eta cross section, and the eta/pi^0 cross section ratio. The cross section and ratio measurements provide essential input for the extraction of fragmentation functions that are needed to access the helicity-dependent parton distribution functions.Comment: 432 authors from 62 institutions, 13 pages, 5 figures, and 3 tables. Submitted to Physical Review D. v2 has minor changes only to update references and reposition figures and tables. All data points plotted in Figs. 2, 4, and 5 are given in Tables I, II, and III, respectivel