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At least 19 recordsLinked to original sources
PubMed2025

Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.

IMPORTANCE: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking. OBJECTIVE: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. DESIGN, SETTING, AND PARTICIPANTS: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025). MAIN OUTCOMES AND MEASURES: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1 - O/E). RESULTS: Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness.

Humans↗
PubMed2026

Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes.

OBJECTIVE: Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease characterized by clinical and molecular heterogeneity, notably in the presence of anti-cyclic citrullinated peptide (CCP) antibodies. Patients with CCP+ RA exhibit more severe disease progression and distinct treatment responses compared to patients with CCP- RA. Although previous studies have investigated cellular and molecular differences between these subtypes, their genetic differences are understudied. METHODS: We leveraged the Rheumatoid Arthritis Comparative Effectiveness Research cohort, comprising 555 patients with CCP+/rheumatoid factor (RF)+ RA and 384 patients with CCP-/RF+ RA. Using a novel framework, we integrated a network-based genome-wide association study (GWAS) with multiomic data to uncover corresponding genetic and molecular differences. RESULTS: We uncovered a significant heritability difference between these disease groups. Network-based GWAS uncovered 14 putative gene modules, including many genes outside the HLA loci, that explained genetic differences between CCP+/RF+ and CCP-/RF+ RA. Heritability partitioning and multivariate expression analyses validated four modules, highlighting novel genetic loci underlying phenotypic differences. Module functional significance was established using multiple orthogonal cohorts, underscoring their biologic relevance. CONCLUSION: Our findings demonstrate the use of network-based approaches in revealing differential genetic risk factors underlying CCP+/RF+ and CCP-/RF+ RA. Disease-associated gene modules detected in synovial tissue were also observed in peripheral blood, indicating joint-specific molecular programs are reflected systemically. This cross-tissue concordance highlights the potential for blood-based assays to capture pathogenic mechanisms active in the joints, enabling practical patient stratification. Our findings highlight why patients with CCP+/RF+ and CCP-/RF+ RA exhibit distinct clinical courses and therapeutic responses, supporting precision-guided treatment strategy development in RA.

Humans↗
PubMed1985

Storage-retrieval processes of normal and learning-disabled children: a stages-of-learning analysis of picture-word effects.

Previous research comparing acquisition performance of learning-disabled and normally achieving children has led to the suggestion that the locus of memory differences lies in either the storage or retrieval components of recall. In this paper we report a free-recall experiment in which a new stages-of-learning model was used to examine the effects of a picture-word manipulation on storage and retrieval differences between nondisabled and disabled grade 2 and 6 children. Although the results of this experiment were consistent with the idea that disabled students are poorer at memory tasks than nondisabled students, the stages-of-learning analysis provided information regarding the precise locus of the deficiencies. Specifically, although disabled and nondisabled children benefited from the presentation of information in pictorial format, normally achieving children were consistently better than their learning-disabled counterparts at storing and learning to retrieve both pictures and words. From a developmental standpoint, the most important finding was that while differences between learning-disabled and normally achieving students at storage remained age invariant, differences in learning to retrieve increased with age. As it turned out, however, differences between disabled and nondisabled children were absent when it came to retaining traces once they had been stored in memory and in retrieval performance between the time a trace was stored and retrieval learning was complete. These results are consistent with previous research in which it has been shown that the ability to learn how to reliably retrieve information that has been stored in memory develops more slowly for disabled than nondisabled children.

Age Factors↗
PubMed1988

[Effects of processing by granular heated beds on the chemical and functional properties of legume grains].

The present research compares the effect of cooking cowpea, canavalia and lupine by pressure cooking and by a granular bed roaster, on chemical and physical characteristics. The wet cooking process was carried out by pressure cooking at 121 degrees C for 30 min at 15 psi, using a bean-to-water ratio of 3 to 1. The cooked samples were dried with heated air (60 degrees C). The granular bed roasting was carried out at 200 and 250 degrees C for contact times of 2 and 2.5 minutes, at a 5 to 1 sand:bean ratio. For this process, a granular bed roaster was designed and constructed. This process induced in the grain temperatures which varied from 90-128 degrees C, and thermic efficiencies which fluctuated between 38 and 60%. The wet and the dry processes did not affect protein and fat content, although available lysine values decreased slightly. The two processes did not affect water absorption and water solubility. The nitrogen solubility index, however, decreased as roasting temperatures increased in the case of the granular bed roaster, and it also decreased in the wet-cooking procedure. Both processes affected color of the cooked flours, with a light orange color, suggesting non-enzymatic browning due to the high temperatures used.

Fabaceae↗
PubMed1989

Internal and external validity in two studies that compared treatment methods.

Research comparing the effectiveness of two treatments offers both strengths and weaknesses for occupational therapy. Although it is worthwhile to determine which of two treatments works best for a particular problem, methodological problems may arise that preclude a valid conclusion. To draw valid conclusions from research, criteria for internal validity and external validity must be satisfied. The two preceding articles in this issue are examples of studies that used between-groups experimental methodology to compare the effectiveness of two different treatments. This paper evaluates the above-mentioned studies on the basis of principles of internal and external validity. One of these studies (Jongbloed, Stacey, & Brighton, 1989) was truly experimental, whereas the other study (Groves & Rider, 1989) was quasi-experimental. Results from both studies were similar because, in each study, both of the treatment groups improved, but there were no significant differences between treatments. Absence of a true control group in both studies presented limitations on the conclusion that both treatments worked equally well.

Analysis of Variance↗
PubMed1992

A comparison of two breathing exercise programs for patients with quadriplegia.

This study compared the use of abdominal weights (AbWts) to inspiratory resistive muscle training (IMT) on selected measures of pulmonary function. Eleven patients, aged 16 to 41 years (mean = 27.8, SD = 8.3) with complete cervical injuries were randomly assigned to either an AbWts or IMT treatment group. Subjects in both treatment groups received daily treatments (five times weekly) for 7 weeks. Forced vital capacity (FVC), inspiratory capacity (IC), maximal voluntary ventilation (MVV), peak expiratory flow rate (PEFR), and inspiratory mouth pressure (PImax) were measured weekly. Analysis of variance for repeated measures showed no difference between the AbWts and IMT treatments; there were significant differences within each respective treatment group for all five variables. Although the data did not support the effectiveness of one method of training over the other, the larger increase in MVV with the IMT protocol may be indicative of an endurance training effect with this protocol. Future research should compare the effects of breathing exercise training to spontaneous recovery of the respiratory muscles in control subjects.

Adolescent↗
PubMed1992

Non-differential underestimation may cause a threshold effect of exposure to appear as a dose-response relationship.

It is generally believed that non-differential misclassification will lead to a bias toward the null-value. However, using one graphical and one numerical example, we show that in situations where underestimation more than overestimation is the problem, non-differential misclassification may lead to a bias away from the null-value for intermediate categories of exposure variables. We show that a true threshold level for an exposure may, subsequently, appear as a dose-response relationship. Underestimation more than overestimation is likely to occur in studies in which self-reports are used to obtain data on activities which respondents voluntarily engage in and which are socially not acceptable or known to be potentially dangerous. Researchers should be aware that both a shown deleterious effect at a low level of exposure and a dose-response relationship may in fact be spurious and due to underestimation of exposure at higher levels.

Bias↗
PubMed2026

Phenacetin inhibited but acetaminophen stabilized partial nitrification/anammox system: Studies on microbial metabolism and resistance genes in biofilm and plastisphere.

Partial nitrification (PN) inhibitors, such as phenacetin (PNCT) and acetaminophen (APAP), ensure a stable nitrite supply for anaerobic ammonium oxidation (anammox). But the unknown impact of inhibitors on anammox limit the application of inhibitors. In addition to the biofilm carriers used in biological nitrogen removal systems, microplastics (MPs) (a type of emerging contaminants) are the common substrate for microbial colonization, even enriched resistance genes (RGs). This research compared the effects of 0.5, 1 and 5 mg/L PNCT or APAP on partial nitrification-anammox (PN/A) biofilm and plastisphere. 1 mg/L PNCT inhibited the nitrogen removal functional bacteria (Nitrosomonas, Candidatus Kuenenia, Candidatus Brocadia and Nitrospira), resulting in the sharp deteriorated performance of PN/A system. 5 mg/L PNCT inhibited multiple metabolism pathways, resulting in the absence of electrons and energy supply of microorganisms. 0.5-1 mg/L APAP maintained the stable operation of PN/A system. Nitrospira abundances declined from 2.8% to 1.1% after 0.5 mg/L APAP exposure. But 5 mg/L APAP inhibited the abundance of amoA and the production of extracellular polymeric substances, which caused the slight fluctuation of PN/A performance. PN inhibitors did not cause the sharp increase of most RGs in biofilm and water. However, MPs exhibited the huge capacity of enriching RGs, which should be removed. This study proposed that 0.5 mg/L of APAP was suitable for the PN/A system to control dosage for practical application.

Biofilms↗
PubMed1976

[Legal abortion and hemostasis. Histological examinations and comparison to post partum hemostasis (author's transl)].

30 women were examined to determine the hemostasis during the legally induced abortion. The blood coagulated in the intervillous spaces while the fetus is removed. Immediately after the termination of the curettment the nidation area is covered by filaments of fibrin and incorporated erythrocytes. More frequent as post partum platelet thrombi occur especially in the area of decidua parietalis. The intravascular findings are similar to post partum changes after the removal of the placenta. Obstruction clots of the spiral arterioles contain fibrin deposits, pletelet thrombi and erythrocytes (mixed form of thrombi). Residual decidua and trophoblast cells are seldom involved in the obturation of the vessels. The traumatic damages of the uterine wall are described (extravascular fibrin deposits, interstitial bleeding, succulent tissue a.s.o.).

Abortion, Legal↗
PubMed1975

Effect of castration on the smooth muscle cells of the internal sex organs of the rat: influence of the smooth muscle on the sympathetic neurons innervating the vas deferens, seminal vesicle and coagulating gland.

Wet weights of vas deferens, seminal vesicle and coagulating gland were reduced by almost 80 to 90% 10 weeks after castration. Endogenous norepinephrine content and dopamine-beta-hydroxylas activity of these tissues were also reduced to the same degree. One week after castration there was approximately a 50% loss in the weight of all three organs. However, this was accompanied by an equal reduction in norepinephrine content and dopamine-beta-hydroxylase activity only in the vas deferens. Two weeks later the degree of reductions in wet weight, norepinephrine content and dopamine-beta-hydroxylase activity was almost identical for all three organs. Treatment of 40-day castrate rats with testosterone (10 mg/kg s.c.) not only restored the wet weights of the internal sex organs to normal but their norepinephrine content and dopamine-beta-hydroxylase activity as well. Castration of immature rats (10-14 days old) resulted in retardation of growth of the vas deferens and seminal vesicle by 90-95%, and similar reductions in norepinephrin content and dopamine-beta-hydroxylase activity, when compared to the tissues of control littermates on the 90th postoperative day. Histological examination of normal and castrate rats indicated that, along with a reduction in epithelial cells, the smooth muscle cells of the vas deferens, seminal vesicle and coagulating gland was markedly reduce in size as well. Administration of testosterone completely reversed these changes. Furthermore, deoxyribonucleic acid content of the seminal vesicle and coagulating gland was reduced by 50% after castration and then restored to control level after testosterone treatment. Taken together, it seems that atrophy of the internal sex organs following castration is a combined effect of reduction in size and number of smooth muscle cells. Therefore, it is concluded that any alteration in the size of smooth muscle cells or loss of such cells of the internal sex organs indirectly influences their sympathetic nerves in such a manner that norepinephrine concentrations, and thereby the density of innervation, are maintained at normal levels.

Animals↗