Locally Preferred Structure and Frustration in Glassforming Liquids: A Clue to Polyamorphism?

We propose that the concept of liquids characterized by a given locally preferred structure (LPS) could help in understanding the observed phenomenon of polyamorphism. ``True polyamorphism'' would involve the competition between two (or more) distinct LPS, one favored at low pressure because of its low energy and one favored at high pressure because of its small specific volume, as in tetrahedrally coordinated systems. ``Apparent polyamorphism'' could be associated with the existence of a poorly crystallized defect-ordered phase with a large unit cell and small crystallites, which may be illustrated by the metastable glacial phase of the fragile glassformer triphenylphosphite; the apparent polyamorphism might result from structural frustration, i. e., a competition between the tendency to extend the LPS and a global constraint that prevents tiling of the whole space by the LPS.Comment: 11, 6 figures, Proceedings of the Conference "Horizons in Complex Systems", Messina; in honor of the 60th birthday of H.E. Stanle

Malnutrition Has No Effect on the Timing of Human Tooth Formation

The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females) consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off) were used to identify the malnourished group (N = 474) while the normal was defined by Z-scores of ≥0 (N = 799). Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05). This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems

Accelerated forgetting in healthy older samples: Implications for methodology, future ageing studies, and early identification of risk of dementia

Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer’s disease (AD). The Verbal Associative Learning & Memory Test (VALMT; McGibbon & Jansari, 2013) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy older participants. Older (60-69yrs) and Younger (19-31yrs) participants were compared. Using VALMT, unrelated word-pairs were learnt to criterion, then cued-recall tested at delays of 5, 30 and 55 minutes. Unique pairs were tested at each delay. Subjective memory complaints data was gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered. VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 minutes (d = 1.32). While ‘fast-learning’ Older participants scored similarly to Younger participants, ‘slow-learning’ Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints. We conclude VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD

Trends in urine sampling rates of general practice patients with suspected lower urinary tract infections in England, 2015–2022: a population-based study

Objectives Inappropriate prescribing of antibiotics is a key driver of antimicrobial resistance. This study aimed to describe urine sampling rates and antibiotic prescribing for patients with lower urinary tract infections (UTIs) in English general practice. Design A retrospective population-based study using administrative data. Setting IQVIA Medical Research Database (IMRD) data from general practices in England, 2015-2022. Participants Patients who have consulted with an uncomplicated UTI in England general practices captured in the IMRD. Outcome measures Trends in UTI episodes (episodes were defined as UTI diagnosis codes occurring within 14 days of each other), testing and antibiotic prescribing on the same day as initial UTI consultation were assessed from January 2015 to December 2022. Associations, using univariate and multivariate logistic regressions, were examined between consultation and demographic factors on the odds of a urine test. Results There were 743 350 UTI episodes; 50.8% had a urine test. Testing rates fluctuated with an upward trend and large decline in 2020. Same-day UTI antibiotic prescribing occurred in 78.2% of episodes. In multivariate modelling, factors found to decrease odds of a urine test included age ≥85 years (0.83, 95% CI 0.82 to 0.84), consultation type (remote vs face to face, 0.45, 95% CI 0.45 to 0.46), episodes in London compared with the South (0.74, 95% CI 0.72 to 0.75) and increasing practice size (0.77, 95% CI 0.76 to 0.78). Odds of urine tests increased in males (OR 1.11, 95% CI 1.10 to 1.13), for those episodes without a same-day UTI antibiotic (1.10, 95% CI 1.04 to 1.16) for episodes for those with higher deprivation status (Indices of Multiple Deprivation 8 vs 1, 1.51, 95% CI 1.48 to 1.54). Compared with 2015, 2016-2019 saw increased odds of testing while 2020 and 2021 saw decreases, with 2022 showing increased odds. Conclusion Urine testing for UTI in general practice in England showed an upward trend, with same-day antibiotic prescribing remaining consistent, suggesting greater alignment to national guidelines. The COVID-19 pandemic impacted testing rates, though as of 2022, they began to recover.</p

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Adaptation of the WHO AWaRe (Access, Watch, Reserve) antibiotic classification to support national antimicrobial stewardship priorities in the UK: findings from a modified Delphi approach to achieve expert consensus

Objectives: In 2017, the WHO introduced the AWaRe (Access, Watch and Reserve) classification of antibiotics to support antibiotic stewardship (AMS) at local, national and global levels. We assessed the categorization of each of the antibiotics for systemic use for antimicrobial stewardship and quality improvement practice across primary and secondary care in the UK, proposing a nationally adapted UK-AWaRe classification. Methods: A four-stage modified Delphi survey was conducted to review the AWaRe classifications in light of antibiotic resistance profiles, antibiotic use and stewardship practice in the UK. Recommendations were iteratively discussed and consensus reached on how to adapt the WHO AWaRe list. Implications of the proposed new categorization for possible antibiotic usage targets were assessed using England national antibiotic consumption data as a case study. Results: Sixty-one experts across the four UK nations participated in the modified Delphi process. Consensus was most easily reached, with least between-expert variation, for Access antibiotics. Seventeen antibiotics differed in categorization when comparing proposed adapted UK-AWaRe classification and the 2023 WHO AWaRe classification. Through the focus group discussions, the importance of clear messaging was highlighted for the proposed move of first-generation cephalosporins into the Access category, a step-change from the 2019 England AWaRe classification, where all cephalosporins were in the Watch category. From the case study analysis of national data in England, Access antibiotics accounted for >60% of human antibiotic use between 2018 and 2022, 69.7% when using the WHO 2023 classification and 63.7% with the proposed UK-adapted 2024 classification. Conclusions: An adapted UK-AWaRe list has been suggested through a consensus-reaching process. This will support national AMS and antibiotic usage targets of the UK antimicrobial resistance 2024–29 national action plan

How old are you now? A new ageing method for nonadults based on dental wear

The main aim of this study is to present a novel method of nonadult (ca. 1–19 years) age‐at‐death estimation using the dental wear of deciduous, mixed deciduous‐permanent, and permanent dentitions, including the incisors, canines, premolars, and first and second molars. The stage‐based method is derived from degrees of dental wear in known‐age (n = 39) and estimated‐age (n = 11) nonadults containing 951 teeth from the predominately 19th century cemetery of Middenbeemster, The Netherlands. The need for such a method is warranted in cases where dental development and/or eruption cannot be assessed for age‐at‐death estimation. As well, by establishing a baseline for normal age‐related nonadult tooth wear, users may better document wear that could be due to extramasticatory behaviours. The regression analysis reveals a strong quadratic correlation—F(2, 47) = 555.1, p R2 = .95, standard error of the estimate = 1.14, residual sum of squares (RSS) = 68.89, predicted residual error sum of squares (PRESS) = 77.67—between age and wear and multivariate adaptive regression splines (R2 = .95, generalised cross validation = 1.67, RSS = 67.68, PRESS = 89.34), which are used to develop an R‐package that users may employ to estimate age‐at‐death from dental wear. The accuracy of this method (78–98%) is evaluated using leave‐one‐out cross‐validation. Analyses of males versus females, deciduous versus permanent, upper versus lower, and anterior versus posterior teeth revealed no apparent reason to warrant separate methods for these groups of separated dentitions. This method fills a disciplinary gap in the understudied area of deciduous and nonadult dental wear and hopes to stimulate much future research. With the R‐package, we also provide the foundation and framework for the development of additional reference populations across different spatiotemporal contexts, to make the method more widely applicable. Bioarchaeolog

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid--base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5--3 mmol/l) and a higher than usual target circuit-Ca2+ (<=0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca2+ in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 +/- 36.5 vs 53 +/- 32.6 hours). Protocol A required additional bicarbonate supplementation (6 +/- 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid--base balance without additional interventions: pH 7.43 (7.40--7.46), Bicarbonate 25.3 (23.8--26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 +/- 2.4 g/day) and in only 30% of group B patients (0.5 +/- 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97--1.45 mmol/l, IQR)