Small Numbers Research Articles

The Potential Value of Prehabilitation for Preventing Delirium in Elective Surgery for Aneurysms of the Abdominal Aorta.

Delirium is a common and serious postoperative complication in elderly patients undergoing abdominal aortic aneurysm (AAA) repair and is associated with a variety of adverse outcomes. Multimodal prehabilitation aims to identify and minimize potential risk factors for delirium and improve overall health. The aim of this study is to investigate the effect of multimodal prehabilitation on delirium incidence in elderly patients undergoing elective repair for AAA. A single-centre cohort analysis was performed in the Netherlands for patients aged ≥70 years, undergoing elective repair for AAA (open surgery and endovascular aortic repair). Prehabilitation was gradually introduced between 2016 and 2019 and offered as standard care from 2019. The program was constructed to optimize overall health and included delirium risk assessment, home-based tailor-made exercises by a physical therapist, nutritional optimization by a dietician, iron infusion in case of anaemia and a comprehensive geriatric assessment by a geriatrician in case of frailty. The primary outcome was incidence of delirium within 30 days after surgery. A total of 81 control and 123 prehabilitation patients were included. A reduction in incidence of delirium was found (11.1% in the control group to 4.9% in the prehabilitation group), with too small numbers to reach statistical significance (p=0.09). Also, patients in the prehabilitation group had a small, non-significant decreased length of hospital stay (4 days) compared to the control group (5 days) (p=0.07). Although no significant differences were found, we carefully conclude that this study provides some support for implementing multimodal prehabilitation for delirium prevention in elderly patients undergoing AAA repair. Further research with larger cohorts is necessary to identify and select patients that would most benefit from prehabilitation.

Prohexadione calcium as a tool to reduce winter pruning in peach tree cultivar Eragil

This work evaluated the efficiency and feasibility of applying calcium prohexadione (PCA) at different times to control the vegetative growth and qualitative aspects of the peach tree cultivar Eragil. The experiment was carried out in the 2021/2022 season in a commercial orchard in the municipality of Ipê, RS. Treatments consisted of applications of PCA at a fixed dose of 20 mL·100 L-1 at different stages of development, as shown: T1 – control (no application); T2 – application in petal fall; T3 – application at petal fall + application 30 DAA (days after the first application); T4 – application after green pruning; T5 – application after green pruning + application 30 DAA; T6 – application at petal fall + application 30 DAA + application 60 DAA. The experimental design was in randomized blocks, with six treatments and four replications. Each plot consisted of four plants; the two central plants were considered useful. Effective fruiting increased in T3. In the evaluations of the number of pruned branches, length of branches, and weight of branches per plant, all results were smaller in T2. In the assessments of number of buds, internode length, and pruning time per hectare, there was also a significant difference, and in the number of buds, T6 had the smallest number. The internode length was the greatest in T3, and the shortest pruning time stood out in T4. Calcium prohexadione effectively controlled the vegetative growth of Eragil peach and can be directed to large areas of the peach crop when labor for pruning is scarce.

유창성 장애의 언어치료 관련 경시적 계수자료의 유연한 분석

In this study, the goal was to apply a flexible and easy-to-manage analysis method through a model that includes a dispersion parameter in the longitudinal analysis method of count data. In the analysis of count data, it may be inconvenient to change the statistical model depending on whether there is under- or over-dispersion. To compensate for these weaknesses, We have applied a statistical method including a dispersion parameter to the statistical model. The count data covered were included in the diagnosis of fluency disorders and the evaluation of the effectiveness of speech therapy. but research on speech-language therapy is limited by being conducted on small numbers of subjects for several reasons. Therefore, statistical analysis methods that work only on large samples, are complex, or require excessive calculations in the model fitting process were not appropriate for the field. With this background, we applied the Conway-Maxwell Poisson model to longitudinal data analysis of fluency disorders. We evaluated whether the model that reflects the level of data dispersion in the model was consistent with the speech therapy data for fluency disorders by comparing it to the existing Poisson mixed model and linear mixed model. In particular, the Conway-Maxwell Poisson model had the advantage of reflecting well when the degree of dispersion was different for each group or specific subgroup.

Considerații pe marginea identificării „procuratorilor” dinactele medievale și premoderne din Transilvania

The documents relating to medieval and pre-modern Transylvania indicate the existence and perpetuation from antiquity of a judicial practice of representation at trials by means of „proxies” (procuratores) designated by the authorization letter (litterae procuratorie). The term procurator was used in parallel with its synonym meaning lawyer (advocatus), being preferred and used with a much higher frequency. The nomination of someone as proxy/assignee was initially witnessed by the places of authentication, later secular institutions get priority. Noblemen frequently appointed educated, specialized, professional people in this position. Initially in small numbers, they come to constitute a social category during the time of the Principality, in numerical and material ascension both at the level of counties and seats and at the urban level. The other large category of legal proxies was occasionally constituted, depending on the circumstances, from family members and their relatives, supplemented by servants, familiars, local rulers, bailiffs, or village judges, sometimes even by serfs living on the estates, by exception.

Problem Çözme Başarısında Büyük ve Küçük Sayıların Rolü

Bu çalışma ikinci sınıf düzeyindeki öğrencilerin büyük ve küçük sayılarla oluşturulmuş problemleri çözebilme becerilerini analiz etmeyi amaçlamaktadır. Bu amaç doğrultusunda ilkokul öğrencilerin problem çözme yeteneklerinin kullanılan sayılarla nasıl değişebileceği incelenmiştir. Karma yöntem olarak tasarlanan araştırmada açımlayıcı sıralı desen tercih edilmiştir. Konya İli Selçuklu İlçesi'nde yer alan dört ayrı ilkokuldan toplam 154 öğrenci ile gerçekleştirilmiştir. Veriler paralel testler ve klinik mülakat ile toplanmıştır. Nicel veriler istatistik programı kullanılarak analiz edilmiştir. Nitel verilerin analizin de ise betimsel analiz yöntemi tercih edilmiştir. Bulgular, problem çözme başarısının kullanılan sayılara güçlü bir şekilde bağlı olduğunu göstermektedir. İkinci sınıf öğrencileri küçük sayılar içeren testlerde daha yüksek puanlar elde etme eğilimindedirler. Bu sonuç, öğrencilerin daha küçük sayılarla ilgili problemlerde daha iyi performans gösterdiğini göstermektedir. Öğrenci yanıtları incelendiğinde, öğrencilerin rutin olmayan problemlerde daha fazla zorlandığı ve bu tür problemlerin daha zor olduğu ortaya çıkmıştır. Klinik mülakat aşamasında öğrencilere farklı büyüklükteki sayılarla ilgili problemler sunulmuş ve çözümleri değerlendirilmiştir. Öğrencilerin genel olarak büyük sayıları içeren problemleri çözmede daha fazla zorlandığı ve bu problemlerin anlama sürecini etkilediği gözlemlenmiştir. Büyük sayılarla çalışırken, öğrenciler genellikle anahtar kelimelere odaklanmıştır. Büyük sayılar içeren problemlerin anlama aşamasından itibaren öğrencileri zorladığı gözlemlenmiştir. Öğrencilere problem çözme öğretimi sunulurken, başlangıçta büyük sayıların karmaşıklığından ziyade daha küçük sayılarla başlamak daha faydalı olabilir.

Examining the efficiency of porcine gastric mucin-coated magnetic beads in extraction of noroviruses from frozen berries

Human norovirus is the leading cause of foodborne gastroenteritis worldwide. Due to the low infectious dose of noroviruses, sensitive methodologies are required to detect and characterize small numbers of viral particles that are found in contaminated foods. The ISO 15216 method, which is internationally recognized for detection of foodborne viruses from high-risk food commodities, is based on viral precipitation, followed by RNA extraction and identification of the viral genome by RT-PCR. Although the ISO 15216 method is efficient, it is time consuming and tedious, does not report on the viral infectivity, and is sensitive to the presence of RT-PCR inhibitors. Norovirus capture by the porcine gastric mucin conjugated magnetic beads (PGM-MB) was developed as an alternative virus recovery method. It relies on the integrity of the viral capsid being able to bind to PGM. PGM contains a variety of histo-blood group antigens (HBGAs) that act as norovirus receptors. Therefore, the PGM-MB method allows for extraction of noroviruses, with potentially intact viral capsids, from complex food matrices. The viral genome can then be released through heat-shock of the captured virus. For this reason, we performed a parallel comparison between the ISO 15216 method and the PGM-MB method in isolation and quantification of noroviruses from frozen raspberries. We have demonstrated that the efficiency of the PGM-MB method in extraction of murine norovirus (MNV) and human norovirus GII.4 from raspberries is equal or better than the ISO 15216 method, while the PGM-MB has fewer steps and shorter turnaround time. Moreover, the PGM-MB method is more efficient in removing the inhibitors prior to RT-PCR analysis.

Photosynthesis in a green alga (zoochlorella), Chlorella cf. vulgaris in the soft coral Sarcophyton sp.

ABSTRACT An undescribed variety of the green alga Chlorella cf. vulgaris was found living in the octocoral (soft coral) Sarcophyton sp., which also has dinoflagellate zooxanthellae. The green alga is present in very small numbers and is capable of photoheterotrophy based on growth in the presence of an inhibitor of photosynthesis, DCMU, with glycerol provided as a carbon source. The presence of zoochlorellae (Chl a + b), in soft corals appears to have been unsuspected. The easily cultured green alga was unicellular, unflagellated and very small, c. 2 to 6 µm in diameter and had a relatively high Chl b content (Chl b/a = 0.379 ± 0.063). Rapid light curves using PAM fluorometry on the cultured cells showed that Yield vs. irradiance had a low maximum yield (Ymax, 0.388 ± 0.0132; Irradiance ½ point, E½Ymax = 139 ± 11.1 µmol photon m–2 s–1). The overall optimum irradiance (Eopt) for the alga was 314 ± 18.8 µmol photon m–2 s–1. The alga can photosynthesize at 50% or more of the optimum rate from 70 to 900 µmol photon m–2 s–1 but would be severely inhibited under full sunlight. Most naturally occurring low irradiance habitats may have a low median irradiance but are exposed intermittently to very high irradiances and so a relatively high Eopt is advantageous in minimizing photochemical damage. Like the green algal symbiont Elliptochloris marina of sea anemones, Chlorella cf. vulgaris is not exclusively marine: it grows better in freshwater medium where it has different photosynthetic characteristics (higher Ymax, Eopt and ETRmax). Chlorella cf. vulgaris appears to be capable of photoheterotrophy and it is not clear if it is a symbiont, a commensal or a parasite.

Irreversibility and nanomaterials shape consequences on peristalsis of magneto hybrid nanofluid via curved configuration with homogeneous–heterogeneous chemical reactions

Over the last decade, research on nanofluids has grown at a breakneck pace. As part of their nanofluid research, researchers have recently attempted to use hybrid nanofluids, made by combining different nanomaterials. The novelty of this analysis is to inspect the consequences of entropy generation on the peristalsis of a hybrid nano-liquid via a curved conduit with homogeneous and heterogeneous chemical reactions. Hybrid nanofluid is formed of copper and iron oxide nanomaterials added to water. Furthermore, the simplified model also considered the Hall current, viscous dissipation, and electrical resistance heating effects. The Hamilton–Crosser thermal conductivity model is used to study the nanomaterials shape effects (i.e. sphere, platelet, and blade) on the thermal features of hybrid nano-liquids. Mathematical expressions for the flow problem are simplified by employing the small wave and Reynolds numbers assumptions, which are then resolved analytically and numerically. Analytical results are used to scrutinize the impacts of several included quantities on the flow and thermal characteristics, chemically reactive concentration, and entropy creation. It is found that with a rise in Hartmann number, the velocity reduces, whereas an improvement is noted in temperature and entropy production for large values of Hartmann number. The noteworthy discoveries indicate that hybrid nano-liquids exhibit enhanced thermal efficiency when compared to conventional nanofluids. Specifically, the introduction of a small quantity of ferrous oxide nanoparticles into the copper–water nanofluid led to less than 2% increase in the thermal transport rate. Additionally, it was observed that spherical-shaped nanoparticles generate more heat in comparison to platelets and blade-shaped nanoparticles. Furthermore, the homogenous reaction parameter and Schmidt number lead to a drop in the concentration profile.

Ignoring Measurement Errors in Social Networks

Abstract We consider peer effect estimation in social network models where some network links are incorrectly measured. We show that if the number or magnitude of mismeasured links does not grow too quickly with the sample size, then standard instrumental variables estimators that ignore these measurement errors remain consistent, and standard asymptotic inference methods remain valid. These results hold even when the link measurement errors are correlated with regressors or with structural errors in the model. Simulations and real data experiments confirm our results in finite samples. These findings imply that researchers can ignore small numbers of mismeasured links in networks.

An engineered antimicrobial peptide as an alternative bioreceptor for the detection of pathogenic Escherichia coli O157:H7

Escherichia coli O157:H7, which can cause acute infections even in extremely small numbers, is the most common pathogen responsible for foodborne illnesses. Both the development of antimicrobial agents and establishment of a sensitive and rapid detection method are essential to prevent foodborne illnesses. In this study, three antimicrobial peptides (AMPs) were derived from magainin 1 and clavanin A through peptide engineering. Subsequently, AMP 3, which showed the highest antimicrobial activity against E. coli O157:H7 in antibacterial activity assays, was screened as a potential candidate bioreceptor. To achieve sensitive and selective detection, a hydrophilic tannic acid (TA)-polyethyleneimine (PEI) hydrogel was modified on a gold electrode, and AMP 3 was immobilized to develop an AMP-based electrochemical sensor. The electrochemical performance of the Au/TA-PEI/AMP 3-based electrochemical biosensor was monitored using cyclic voltammetry and differential pulse voltammetry. The limit of detection of the Au/TA-PEI/AMP 3 biosensor was determined to be 3.4 colony-forming units (CFU)/mL, with a linear detection range of 101–105 CFU/mL. In addition, the biosensor was applied to quantitatively detect E. coli O157:H7 in milk samples, achieving excellent recovery rates ranging from 89.1 to 122.0 %. Overall, the developed AMP-based biosensor exhibits a good selectivity and sensitivity in the detection of E. coli O157:H7; these features render it a potential tool for detecting bacteria that pose a threat to public health and safety.

Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression

ObjectiveWe conducted an open-label clinical trial (“Bio-K”) using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission. Here, we report the clinical efficacy and side effect outcomes of Bio-K. MethodsAcross 4 US sites, 75 patients ages 18–65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period. Key exclusion criteria were psychotic symptoms, significant substance abuse, unstable medical conditions, and any use of cannabis. Pre-existing antidepressant medication was maintained. Primary outcome was remission as measured by Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcome of 50 % reduction in Beck Suicide Scale score. Safety monitoring and varying durations of infusions were also key parameters. ResultsUsing remission as MADRS score <10, after 3 infusions 52 % achieved remission, with 67 % achieving response. Of those achieving response after a single infusion, 66 % (22 of 33) reached remission after 3 infusions, while 40 % (16 of 40) non-responders after the first infusion went on to achieve remission after 3 infusions. Only 20 % of non-responders after 2 infusions achieved remission. Most (81 %) participants had significant suicidal ideation at baseline; of these, two-thirds (67 %) experienced at least a 50 % reduction in suicidality. Side effects were minimal. Uniquely, we had three different types of infusion categories, with individuals receiving: (1) slow (100-min) infusions only or (2) regular (40-min) infusions only or (3) a mix of infusion durations. These three infusion groups showed comparable safety and efficacy. Exploration of clinical factors revealed no link between BMI, age, or gender to remission. ConclusionsThe consistency of outcomes across 4 clinical sites and across multiple instruments, suggests high acute efficacy and safety of IV ketamine for serious depressive episodes. Duration of infusion did not alter outcomes. Meaningfully, 40 % of non-responders after a single infusion did reach remission subsequently, while only 20 % of non-responders after 2 infusions achieved remission, suggesting early response is suggestive for eventual remission. Our data on varying ketamine infusion duration adds novel insights into the clinical administration of this new treatment for refractory and severe patients. Our limitations included a lack of a control group, necessitating caution about conclusions of efficacy, balanced by the utility of reporting “real-world” outcomes across multiple clinical sites. We could also not separately analyze results for bipolar disorder due to small numbers. Together, the Bio-K clinical results are promising and provide significant sample sizes for forthcoming biological markers analyses.

Thoughts on Plautine Style, with Special Reference to Archaism and Colloquialism

This article discusses style in Plautus. In order to do so objectively, we need to look at distribution patterns; a phenomenon can be considered poetic or colloquial if (a) it is restricted to poetry or comedy, (b) a parallel corpus of the same time period has an equivalent expression, and (c) this distribution is statistically significant. The main problem with applying such an approach to Plautus is that he makes up 60% of early Latin (with Terence giving us another 15%); other texts are not always suitable for comparison: inscriptions may be short, highly formal, or hard to date, Cato’s work on agriculture is extremely technical, and fragments of early drama are often quoted by grammarians who are more interested in what is possible than in what is normal. However, we can compare Plautus with Plautus, insofar as we can compare different stock characters, different metres, or different sub-genres within comedy.Loss of final –s and iambic shortening seem to more common in colloquial passages, with a preponderance in iambic lines, a smaller number in long verses, and the smallest number in polymetric song. Within morphology, subjunctives of the type siem and mediopassive infinitives ending in –ier are strongly preferred at line end, out of metrical convenience; they are already archaic in Plautus, but still employed so frequently that not every individual instance is stylistically significant. Pronominal accusative and ablative forms like med and ted are also already old-fashioned and used mostly for metrical reasons; they, too, occur so commonly that not every instance is significant. Other morphological features look archaic from a classical perspective, but are still normal in Plautus; this is the case for the second-person medio-passive ending –re and the fourth-conjugation imperfect in –ibam. Genitive plural forms of the second declension mostly end in –orum; the older –um is largely restricted to fixed collocations, which are presumably stylistically unmarked.On the other hand, disyllabic genitive endings of the first declension (type familiai) were already archaic in Plautus’ day; they are rare and thus always used for stylistic effect. Within syntax, not all features that have traditionally been described as colloquial really do form part of a lower register. The ellipsis of subject accusatives in the accusative-and infinitive construction is driven by pragmatic and morphosyntactic factors rather than by stylistic considerations. Sentence length and complexity is lower in Plautus than in classical prose, but this is a feature of spoken language rather than of lower register. And finally, outside some common collocations, the ablative absolute is restricted to specific high-register contexts, such as prayers or battle reports.When Plautus wants to be colloquial, he can use features from phonology to syntax, but when he wants to sound archaic, he limits himself to morphology (and lexical features). This should not come as a surprise: Plautus had access to colloquial language on a daily basis, but would encounter archaic texts mostly in written form; here, morphological and lexical features are the ones which are most noticeable and easiest to imitate.

PHYSICAL ACTIVITY AND THE DEVELOPMENT OF DEMENTIA BETWEEN AGES 70 AND 95

Abstract Whilst the protective effects of physical activity (PA) on cognitive function are well documented, it remains unclear if the preventive effect continues irrespective of advancing age. This study examines the association between physical activity and subsequent dementia between ages 70-95. The Jerusalem Longitudinal Study (1990-2023) prospectively follows a representative community-dwelling cohort born 1920-21, assessed at home visit during 1990,1998, 2005, 2010, 2015 at ages 70, 78, 85, 90, and 95 (n=430, 715, 1136, 660, 492) respectively. Comprehensive assessment included Mini Mental State Examination (MMSE) defining dementia (≤23/30), and PA assessment, dichotomized to Active (PA-A) (&amp;gt;4hours a week) versus Sedentary (PA-S) (&amp;lt; 4 hours weekly). Logistic regression analyses determined Odds Ratios (OR) for developing dementia, adjusted for baseline MMSE, gender, education, depression and BADL. At ages 70, 78, 85, 85, 90, and 95 the frequency of PA-A was 45.9%, 69.7%, 48.7%, 9.5%, 11.9%; and frequency of dementia among PA-A vs. PA-S was 1.7% vs. 5.0%, 1.7% vs. 12.6%, 10.6% vs. 48.5%, 8.6% vs. 35.5%, 18.3% vs. 29.9% (all p&amp;lt; 0.0001 except age 70 due to small numbers) respectively. Adjusted ORs ratios among PA-A at baseline for subsequently developing dementia between ages 78-85, 85-90, 90-95 were: OR 0.44 (95%CI 0.20-0.98); OR 0.52 (95%CI 0.30-0.90); OR 0.37 (95%CI 0.13-1.07) respectively. Our findings show that physical activity is associated with reduced development of dementia throughout follow-up between ages 70-95, and support the hypothesis that there is no upper age-limit to the beneficial effects of PA on cognition.

Prevalence of Incidental Extraspinal Findings on MR Imaging of the Lumbar Spine in Adults: A Systematic Review and Meta-analysis.

Low back pain is common worldwide. MR imaging may identify extraspinal findings that are not related to the proposed clinical question. The prevalence of extraspinal incidental findings and their clinical significance has not been well-established. This review aimed to evaluate the prevalence of extraspinal findings on MR imaging of the lumbar spine in adults and the prevalence of clinically significant incidental findings. A systematic search of MEDLINE and EMBASE was performed, including studies published before June 14, 2023. Studies presenting a prevalence of extraspinal findings in patients 16 years of age or older were included. A random effects meta-analysis was used to generate composite prevalence measures of extraspinal findings, patients with extraspinal findings, and clinically significant findings. Sixteen studies were included in this meta-analysis, with a total of 19,593 patients and 6,006 extraspinal incidental findings. The overall prevalence of extraspinal findings was 19.9% (95% CI, 11.1%-30.7%). Overall, 26.7% of patients had an extraspinal finding identified (95% CI, 14.8%-40.6%). The most common subgroup of extraspinal findings was genitourinary findings in males (27.1%; 95% CI, 25.6%-28.8%). Data from 8 studies demonstrated the prevalence of clinically significant findings at 5.4% (95% CI, 3.2%-8.1%). Retrospective populations with small numbers of participants in clinically relevant subgroups may result in heterogeneity and imprecision within composite outcome measures. Extraspinal findings are common, detected in more than one-quarter of patients. Five percent of findings are clinically significant and may require further action.

Insight into the significance of CD8+ tumor-infiltrating lymphocytes in squamous cell lung cancer.

Although there are great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. We objectively investigated the prognostic significance of tumor-infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ-LC). Among patients who underwent surgical resection of SQ-LC in 2011-2017, 100 patients with pathological stage IA3-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse-free survival was analyzed using a Kaplan-Meier survival analysis and multivariate analyses using Fine-Gray and Cox proportional hazards models. The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29-1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21-1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91-7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. Our study provided partial but important information on the significance of CD8 + TILs in SQ-LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Final Results from RIBBIT: A Randomized Phase III Study to Evaluate Efficacy and Quality of Life in Patients with Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Receiving Ribociclib in Combination with Endocrine Therapy or Chemotherapy with or without Bevacizumab in the First-Line Setting

Background: We investigated the efficacy and health-related quality of life (HRQoL) in patients receiving either ribociclib plus endocrine therapy (ET) or chemotherapy with/without bevacizumab as first-line treatment of metastatic hormone receptor (HR)-positive, HER2-negative breast cancer (BC). Patients and Methods: In this randomized, phase III study (RIBBIT), 38 patients diagnosed with metastatic HR-positive, HER2-negative BC with presence of visceral metastases recruited between May 2018 and December 2020 were randomly assigned in a 1:1 ratio to either arm A (ribociclib + ET) or arm B (chemotherapy with/without bevacizumab) at 12 sites in Germany. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS), patient-reported HRQoL, and frequency and type of adverse events. During study conduction, the recruitment rate was persistently and considerably lower than originally expected. Therefore, the recruitment was ended prematurely. The study was initially designed to enroll and randomize 158 patients. Results: Median [95% CI] PFS was 27.3 months [19.1 – NA, parameter not estimable] in arm A and 15.8 months [8.2 – NA] in arm B. Complete responses were achieved only in arm A (n = 2, 10.5%). The ORR [95% CI] between arm A (57.9% [33.5–79.7]) and arm B (52.6% [28.9–75.6]) was comparable. Median OS [95% CI] was not reached in arm A, while in arm B median OS was 28.4 months [25.0 – NA]. Patients in arm A reported less burden by side-effects. No new safety signals emerged. Conclusion: Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency toward a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

The functional trajectories of older women having surgery for gynaeoncology cancer: A single site prospective observational study

IntroductionPopulation aging longevity and advances in robotic surgery suggest that increasing numbers of older women having gynaeoncological surgery is likely. Postoperative morbidity and mortality are more common in older than younger women with the age-associated characteristics of multimorbidity and frailty being generally predictive of worse outcome. Priorities that inform treatment decisions change during the life course: older patients often place greater' value on quality-of-life-years gained than on life expectancy following cancer treatments. However, data on post-operative cognition, frailty, or functional independence is sparse and not routinely collected. This study aimed to describe the clinical characteristics and trajectory of functional change of older women in the 12 months following gynaeoncological surgery and to explore the associations between them. Materials and MethodsThe prospective observational cohort study recruited consecutive women aged 65 or over scheduled for major gynaeoncologic surgery between July 2017 and April 2019. Baseline data on cancer stage, multimorbidity, and geriatric syndromes including cognition, frailty, and functional abilities were collected using standardised tools. Delirium and post-operative morbidity were recorded. Post hospital assessments were collected at 3-, 6-, and 12-months. ResultsOverall, of 103 eligible participants assessed pre-operatively, most (77, 70%) remained independent in personal care at all assessments from discharge to 12 months. Functional trajectories varied widely over the 12 months but overall there was no significant decline or improvement for the 85 survivors. Eleven experienced a clinically significant decline in function at six months. This was associated with baseline low mood (P < 0.05), albeit with small numbers (6 of 11). Cognitive impairment and frailty were associated with lower baseline function but not with subsequent functional decline. DiscussionThere was no clear clinical profile to identify the minority of older adults who experienced a clinically significant decline six months after surgery and for most, the decline was transient. This may be helpful in enabling informed patient consent. Assessment for geriatric syndromes and frailty may improve individual care but our findings do not indicate criteria for segmenting the patient population for selective attention. Future work should focus on causal pathways to potentially avoidable decline in those patients where this is not determined by the cancer itself.

Calculating Thermodynamic Factors for Diffusion Using the Continuous Fractional Component Monte Carlo Method.

Thermodynamic factors for diffusion connect the Fick and Maxwell-Stefan diffusion coefficients used to quantify mass transfer. Activity coefficient models or equations of state can be fitted to experimental or simulation data, from which thermodynamic factors can be obtained by differentiation. The accuracy of thermodynamic factors determined using indirect routes is dictated by the specific choice of an activity coefficient model or an equation of state. The Permuted Widom's Test Particle Insertion (PWTPI) method developed by Balaji et al. enables direct determination of thermodynamic factors in binary and multicomponent systems. For highly dense systems, for example, typical liquids, it is well known that molecular test insertion methods fail. In this article, we use the Continuous Fractional Component Monte Carlo (CFCMC) method to directly calculate thermodynamic factors by adopting the PWTPI method. The CFCMC method uses fractional molecules whose interactions with their surrounding molecules are modulated by a coupling parameter. Even in highly dense systems, the CFCMC method efficiently handles molecule insertions and removals, overcoming the limitations of the PWTPI method. We show excellent agreement between the results of the PWTPI and CFCMC methods for the calculation of thermodynamic factors in binary systems of Lennard-Jones molecules and ternary systems of Weeks-Chandler-Andersen molecules. The CFCMC method applied to calculate the thermodynamic factors of realistic molecular systems consisting of binary mixtures of carbon dioxide and hydrogen agrees well with the NIST REFPROP database. Our study highlights the effectiveness of the CFCMC method in determining thermodynamic factors for diffusion, even in densely packed systems, using relatively small numbers of molecules.

Prevalence and burden of vitiligo in Africa, the Middle East and Latin America.

Vitiligo is a common chronic autoimmune disorder characterized by skin and hair depigmentation that affects 0.5%-2.0% of the global population. Vitiligo is associated with diminished quality of life (QoL) and psychosocial burden. The burden of vitiligo may vary based on skin tone and cultural differences as well as geographical variations in disease awareness, societal stigma, healthcare systems and treatment options. Data on the burden and management of vitiligo in Africa, the Middle East and Latin America are scarce. Literature searches using terms covering vitiligo in Africa, the Middle East and Latin America were conducted using PubMed to identify relevant publications that focused on disease prevalence and burden, QoL and psychosocial impact and disease management between 2011 and 2021. Most of the reviewed studies were conducted in the Middle East, and most Latin American studies were from Brazil. Most studies involved small patient numbers and may not be generalizable. Reported prevalence of vitiligo ranged from 0.18% to 5.3% in Africa and the Middle East, and from 0.04% to 0.57% in Latin America. In several studies, prevalence was higher among female participants. Generally, non-segmental vitiligo was the dominant clinical variant identified and the age at onset varied widely across studies. Common comorbidities include autoimmune diseases such as Hashimoto's thyroiditis, alopecia areata and diabetes. Few treatment guidelines exist in these regions, with the exceptions of guidelines published by the Brazilian and Argentinian Societies of Dermatology. There is a clear unmet need for large epidemiological studies with uniform methodology to accurately ascertain the true prevalence of vitiligo in Africa, the Middle East and Latin America. Additional data on vitiligo burden and management in Africa and Latin America are also needed, along with local disease management guidelines that consider genetic variation, psychosocial burden and socioeconomic diversity in all 3 regions.

Diversity and seasonal dynamics analysis of the blood-sucking mosquitoes fauna (Diptera, Culicidae) of the Tavdinsky district of the Sverdlovsk region

This article provides data on the species diversity and seasonal dynamics of blood-sucking mosquitoes (Diptera, Culicidae), which are important vectors of various infectious and invasive diseases. As a result of the research conducted during several seasons from 2020 to 2022, it was revealed that 11 species of mosquitoes belonging to the genera Anopheles, Aedes and Culiseta live on the territory of the Tavdinsky district of the Sverdlovsk region. When comparing the number of culicids for all seasons, a correlation was revealed between hydrological, weather conditions and the intensity of insect summer. The optimal level of precipitation during the year provides enough breeding sites for mosquito larvae. The 2022 season was favorable for the development and summer of mosquitoes, in which heavy precipitation contributed to a vast area of reservoirs necessary for the development of insects. The smallest number was observed in 2021. As a result of low rainfall, severe frosts in winter, cold spring and arid, hot summer, there was a reduction in the number of mosquitoes. The results of the study allow a deeper understanding of the ecology of mosquitoes in this region, their activity in different seasons and their potential role in the transmission of infections. This work is important for the development of effective strategies for controlling mosquitoes and preventing diseases associated with their bites.