Month: February 2025

Global societies are facing disruption, and agricultural output is suffering due to the increasing frequency and intensity of droughts and heat waves, both consequences of climate change. Epigallocatechin molecular weight We recently observed that under conditions of simultaneous water deficit and heat stress, the stomata on soybean leaves (Glycine max) exhibited closure, contrasting with the open stomata observed on the flowers. This unique stomatal response was paired with differential transpiration, higher in flowers and lower in leaves, which resulted in flower cooling during combined WD and HS conditions. enzyme-based biosensor Soybean pods subjected to a combination of water deficit (WD) and high salinity (HS) stressors adopt a similar acclimation response, leveraging differential transpiration, to lower their internal temperatures by about 4 degrees Celsius. Our findings further indicate that elevated levels of transcripts involved in the degradation of abscisic acid are linked to this response, and obstructing pod transpiration through stomata closure results in a notable increase in internal pod temperature. Our RNA-Seq study of developing pods in plants experiencing both water deficit and high temperature stresses demonstrates a distinct pod response compared to leaves or flowers. We observed a decrease in the number of flowers, pods, and seeds per plant under water deficit and high salinity stress; however, there was an increase in seed mass compared to plants only under high salinity stress, and fewer seeds exhibited suppressed or aborted development under combined stress compared to high salinity stress alone. Analysis of soybean pods subjected to the combined effects of water deficit and high salinity has highlighted differential transpiration, a process that demonstrably reduces the impact of heat stress on seed production.

Liver resection procedures are increasingly employing minimally invasive techniques. This research aimed to compare the surgical outcomes of robot-assisted liver resection (RALR) and laparoscopic liver resection (LLR) for liver cavernous hemangioma, alongside evaluating the treatment's practical application and safety.
Between February 2015 and June 2021, a retrospective analysis was conducted at our institution of prospectively collected data concerning consecutive patients who underwent RALR (n=43) and LLR (n=244) for liver cavernous hemangioma. An analysis, employing propensity score matching, compared patient demographics, tumor characteristics, and the outcomes of intraoperative and postoperative procedures.
The RALR group demonstrated a statistically significant (P=0.0016) shorter average length of postoperative hospital stay. Overall operative time, intraoperative blood loss, blood transfusion rates, conversion to open surgery, and complication rates showed no statistically significant differences between the two groups. biocultural diversity No perioperative deaths occurred. Statistical analyses employing multivariate methods revealed that hemangiomas located in posterosuperior liver segments and those in close proximity to major vascular structures independently correlated with increased blood loss during surgical procedures (P=0.0013 and P=0.0001, respectively). In patients harboring hemangiomas adjacent to critical vascular pathways, no noteworthy distinctions in perioperative results emerged between the two groups, the sole difference being intraoperative blood loss, which was considerably less in the RALR group compared to the LLR group (350ml versus 450ml, P=0.044).
RALR and LLR were found to be both safe and applicable for treating liver hemangioma in carefully selected patients. In the context of liver hemangioma patients exhibiting proximity to major vascular structures, RALR was associated with a more significant reduction in intraoperative blood loss than conventional laparoscopic surgical techniques.
The treatment of liver hemangioma in carefully selected patients demonstrated the safety and feasibility of RALR and LLR. In the presence of liver hemangiomas strategically near vital blood vessels, the RALR procedure yielded better results in minimizing intraoperative blood loss compared to standard laparoscopic surgery.

Patients with colorectal cancer experience colorectal liver metastases in about half of the diagnosed cases. Minimally invasive surgery (MIS), while increasingly favored for resection among this patient group, suffers from a paucity of specific guidelines on its hepatectomy application in this context. An expert panel encompassing various disciplines was formed to produce evidence-driven guidelines for determining the best course of action, either MIS or open, in the removal of CRLM.
A thorough examination of the literature explored the efficacy of minimally invasive surgery (MIS) relative to open techniques in the excision of isolated liver metastases from colorectal cancers, focusing on two key questions (KQ). Expert subject matter specialists employed the GRADE methodology to create evidence-based recommendations. Beyond that, the panel outlined suggestions for subsequent research projects.
Two key questions the panel considered were those of staged versus simultaneous resection strategies for resectable colon or rectal metastases. The panel conditionally recommended MIS hepatectomy for staged and simultaneous resection, contingent upon surgeon-determined safety, feasibility, and oncologic efficacy, assessing individual patient characteristics. The recommendations' underpinning evidence had a low and very low certainty rating.
These evidence-based recommendations offer surgical guidance for CRLM, emphasizing that each case necessitates individual consideration. Focusing on the identified research needs could help to further refine the evidence and lead to improved future guidelines for applying MIS techniques within CRLM treatment.
These evidence-based recommendations for CRLM surgical procedures underscore the significance of personalized care for each patient, offering guidance for surgical decision-making. To refine the evidence and enhance future CRLM MIS treatment guidelines, pursuing the identified research needs is crucial.

Thus far, there has been a dearth of knowledge regarding the health-related behaviors of patients with advanced prostate cancer (PCa) and their partners concerning treatment and the disease itself. This study sought to determine the characteristics of treatment decision-making (DM) preferences, general self-efficacy (SE), and fear of progression (FoP) in couples managing advanced prostate cancer.
In an exploratory study, 96 patients with advanced prostate cancer and their spouses responded to the multiple-choice versions of the Control Preferences Scale (CPS) relating to decision-making, the General Self-Efficacy Short Scale (ASKU), and a shortened Fear of Progression Questionnaire (FoP-Q-SF). Correlations were subsequently drawn after evaluating patients' spouses using the corresponding questionnaires.
Active DM was selected by over 60% of patients (61%) and spouses (62%), proving its popularity. A preference for collaborative DM was exhibited by 25% of patients and 32% of spouses, while 14% of patients and 5% of spouses favored passive DM. Spouses exhibited significantly higher FoP levels compared to patients (p<0.0001). Patients and spouses exhibited no substantial variations in SE; the p-value was 0.0064. The relationship between FoP and SE was negatively correlated among both patient groups and their spouses (r = -0.42 and p < 0.0001 for patients, and r = -0.46 and p < 0.0001 for spouses). DM preference exhibited no relationship with SE and FoP metrics.
The presence of high FoP and low general SE scores is interconnected among patients with advanced PCa and their spouses. Female spouses, compared to patients, appear to have a higher prevalence of FoP. A strong accord frequently exists between couples regarding their active part in DM treatment.
The internet address www.germanctr.de leads to a website. The requested document, with the reference DRKS 00013045, must be returned.
The website www.germanctr.de exists. Kindly return the document, DRKS 00013045.

Intracavitary and interstitial brachytherapy for uterine cervical cancer demonstrates slower implementation speeds compared to image-guided adaptive brachytherapy, potentially due to the more invasive nature of inserting needles directly into the tumor. In an effort to expedite the practical application of intracavitary and interstitial brachytherapy for uterine cervical cancer, the Japanese Society for Radiology and Oncology supported a first hands-on seminar on image-guided adaptive brachytherapy, held on November 26, 2022. This article analyzes this hands-on seminar's influence on participants' levels of confidence in starting intracavitary and interstitial brachytherapy, examining changes from before to after the seminar.
The seminar's schedule included morning lectures on intracavitary and interstitial brachytherapy, followed by hands-on training in needle insertion and contouring, and practical sessions on dose calculation using the radiation treatment system in the evening. Participants' confidence levels in performing intracavitary and interstitial brachytherapy were evaluated using a questionnaire, both before and after the seminar, with responses ranging from 0 to 10 (higher numbers signifying greater confidence).
Eleven institutions contributed fifteen physicians, six medical physicists, and eight radiation technologists who attended the meeting. Before the seminar, the median confidence level was 3 (0-6). Following the seminar, the median confidence level saw a remarkable improvement to 55 (3-7), representing a statistically significant difference (P<0.0001).
The impact of the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer is anticipated to be a surge in confidence and motivation amongst attendees, accelerating the implementation of these procedures.

There is ongoing discussion about the appropriateness of wound drainage as a post-total knee arthroplasty (TKA) procedure. The research sought to determine the impact of postoperative suction drainage on the early recovery of patients who underwent TKA procedures, augmented by concurrent intravenous tranexamic acid (TXA) administration.
Systematic intravenous tranexamic acid (TXA) was used for one hundred forty-six patients undergoing primary total knee arthroplasty (TKA), and these patients were randomly allocated into two groups in a prospective manner. Subjects in the initial study group (n=67) received no suction drainage, unlike the second control group (n=79), who had a suction drain. Both cohorts' perioperative hemoglobin levels, blood loss, complication rates, and duration of hospital stays were examined. Preoperative and postoperative range of motion, as well as Knee Injury and Osteoarthritis Outcome Scores (KOOS), were measured and compared at the six-week follow-up appointment.
Higher hemoglobin levels were present in the study group preoperatively and during the first two days after surgery. There was no difference in hemoglobin between the groups on the third day. A comparison of blood loss, length of hospitalization, knee range of motion, and KOOS scores revealed no substantial disparities between the groups at any time. The study group revealed complications in one patient, and ten patients in the control group experienced complications that called for additional treatments.
Early postoperative results for TKA with TXA were unaffected by the use of suction drains.
The introduction of suction drains post-TKA with TXA did not influence early recovery parameters.

The highly disabling neurodegenerative disease, Huntington's disease, is recognizable by a combination of cognitive, motor, and psychiatric dysfunction. Th1 immune response The causal genetic mutation in huntingtin (Htt, also known as IT15), located on chromosome 4's p163 region, directly results in a broadened triplet encoding polyglutamine. Expansion is a constant companion of the disease, manifesting prominently when repeat counts exceed 39. HTT, the gene responsible for encoding the huntingtin protein, carries out a wide array of important biological tasks within the cell, specifically in the nervous system. The exact method by which this substance causes harm remains unclear. According to the one-gene-one-disease model, the dominant theory attributes toxicity to the widespread aggregation of the HTT protein. The aggregation of mutant huntingtin (mHTT) is, in fact, accompanied by a drop in the concentration of wild-type HTT. Neurodegenerative disease onset and progression may be plausibly linked to a loss of wild-type HTT, functioning as a pathogenic contributor. Apart from the huntingtin protein, various other biological pathways, including those of autophagy, mitochondria, and other crucial proteins, are also impacted in Huntington's disease, possibly explaining the diversity of disease presentations and clinical characteristics amongst individuals affected. Future efforts in identifying specific Huntington subtypes are necessary to create biologically targeted therapies that correct the relevant biological pathways, rather than solely focusing on eliminating the common denominator of HTT aggregation, since one gene does not equate to one disease.

The rare, fatal disease of fungal bioprosthetic valve endocarditis requires significant medical attention. infectious bronchitis Vegetation within bioprosthetic valves was infrequently associated with severe aortic valve stenosis. The most positive outcomes in endocarditis cases arise from surgical procedures that incorporate antifungal treatment, a crucial element considering the role of biofilm in persistent infections.

A triazole-based N-heterocyclic carbene iridium(I) cationic complex, [Ir(C8H12)(C18H15P)(C6H11N3)]BF408CH2Cl2, with a tetra-fluorido-borate counter-anion, has been both synthesized and its structure determined. The iridium atom, residing centrally within the cationic complex, exhibits a distorted square-planar coordination geometry, established by a bidentate cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene ligand, and a triphenylphosphane ligand. C-H(ring) interactions, integral to the crystal structure, orchestrate the spatial arrangement of the phenyl rings; furthermore, the cationic complex engages in non-classical hydrogen-bonding inter-actions with the tetra-fluorido-borate anion. A triclinic unit cell, housing two structural units and incorporating di-chloro-methane solvate molecules with an occupancy of 0.8, encapsulates the crystal structure.

Deep belief networks are consistently used in the domain of medical image analysis. The model is prone to dimensional disaster and overfitting due to the high-dimensional and small-sample-size nature of medical image datasets. The standard DBN emphasizes speed and efficiency, but often neglects the necessity for explainability, which is paramount in medical image analysis applications. A sparse, non-convex explainable deep belief network is presented in this paper, formed by the fusion of a deep belief network and non-convex sparsity learning techniques. To achieve sparsity, a non-convex regularization term and a Kullback-Leibler divergence penalty are integrated into the DBN architecture, resulting in a network with sparse connections and sparse activations. This approach simplifies the model's structure while boosting its capacity for broader application. Explainability necessitates selecting crucial features for decision-making through a feature back-selection method based on the row norms of weights in each layer's matrix after the training of the network has been completed. Our model, when applied to schizophrenia datasets, achieves the best outcome among various typical feature selection models. The discovery of 28 functional connections, highly correlated with schizophrenia, provides a solid foundation for treating and preventing schizophrenia, and assurance of methodology for other similar brain disorders.

Parkinson's disease necessitates a dual approach encompassing disease-modifying and symptomatic treatments to address its various challenges effectively. Advancements in our comprehension of Parkinson's disease pathology, and fresh perspectives on genetics, have uncovered promising new areas for the development of pharmacological therapies. The road from groundbreaking discovery to medicinal approval, however, is fraught with difficulties. Central to these problems are the issues of selecting suitable endpoints, the lack of accurate biomarkers, challenges associated with precise diagnostics, and other difficulties frequently encountered in pharmaceutical research. However, the health regulatory bodies have offered tools to provide direction for the development of pharmaceutical products and to address these issues. click here The Critical Path for Parkinson's Consortium, a public-private initiative under the Critical Path Institute umbrella, has the principal aim of progressing these Parkinson's disease trial drug development tools. This chapter centers on the successful application of health regulators' tools in advancing drug development for Parkinson's disease and other neurodegenerative illnesses.

Studies are revealing a potential connection between intakes of sugar-sweetened beverages (SSBs), containing various forms of added sugar, and an increased probability of cardiovascular disease (CVD). However, the effect of fructose from other dietary sources on the risk of cardiovascular disease remains unresolved. Through a meta-analysis, we examined potential dose-response relationships between the consumption of these foods and cardiovascular disease, encompassing coronary heart disease (CHD), stroke, and associated morbidity and mortality. A systematic review of the literature across PubMed, Embase, and the Cochrane Library was conducted, encompassing all records from their respective inception dates through February 10, 2022. In our investigation, we included prospective cohort studies that examined the impact of at least one dietary source of fructose on the risk of CVD, CHD, and stroke. Sixty-four included studies' data facilitated the calculation of summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest intake category relative to the lowest, alongside dose-response modelling. Analysis of various fructose sources revealed a positive association between sugar-sweetened beverage consumption and cardiovascular disease. A 250 mL/day increase in intake was linked to hazard ratios of 1.10 (95% CI 1.02–1.17) for CVD, 1.11 (95% CI 1.05–1.17) for CHD, 1.08 (95% CI 1.02–1.13) for stroke morbidity, and 1.06 (95% CI 1.02–1.10) for CVD mortality. This association was unique to sugar-sweetened beverage intake. Conversely, the results indicated protective associations for three dietary items. Fruit consumption was linked to lower CVD morbidity (HR 0.97; 95% CI 0.96, 0.98) and mortality (HR 0.94; 95% CI 0.92, 0.97). Yogurt consumption was also related to lower CVD mortality (HR 0.96; 95% CI 0.93, 0.99), and breakfast cereal consumption demonstrated a particularly strong protective effect on CVD mortality (HR 0.80; 95% CI 0.70, 0.90). Except for the J-shaped pattern of fruit consumption impacting CVD morbidity, all other relationships between these factors were linear. The lowest CVD morbidity occurred at a fruit intake of 200 grams per day, and no protective effect was present above 400 grams daily. The study's findings reveal that the adverse links between SSBs and CVD, CHD, and stroke morbidity and mortality are not applicable to fructose from other dietary sources. Cardiovascular consequences of fructose intake demonstrated a variation dependent on the composition of the food matrix.

People in today's world spend an increasing amount of time in cars, and the potential for formaldehyde-related health concerns should not be ignored. Utilizing solar light to drive thermal catalytic oxidation is a potential approach to purifying formaldehyde emissions from cars. MnOx-CeO2, prepared as the central catalyst via a modified co-precipitation process, underwent in-depth characterization of its fundamental properties, including SEM, N2 adsorption, H2-TPR, and UV-visible absorbance.

We examined the performance of logistic regression models across training and test patient groups. The Area Under the Curve (AUC) associated with each week's sub-region was used for the analysis and the results were compared to models trained on baseline dose and toxicity information alone.
The radiomics-based models, in the current study, exhibited a better capacity for predicting xerostomia than the standard clinical predictors. The baseline parotid dose and xerostomia scores, when utilized in a model, determined an AUC.
Models built using radiomics features from the 063 and 061 parotid scans for xerostomia prediction at 6 and 12 months post-radiotherapy demonstrated a maximum AUC, significantly outperforming models based on the entire parotid gland's radiomics.
The values of 067 and 075 were, respectively, observed. In general, across all sub-regions, the peak AUC was observed.
Models 076 and 080 served to predict xerostomia conditions at the 6-month and 12-month follow-up time points. Within the initial fortnight of treatment, the cranial portion of the parotid gland consistently exhibited the highest area under the curve.
.
Our study's results highlight that radiomics variations within parotid gland sub-regions contribute to a more timely and accurate prognosis for xerostomia in patients with head and neck cancer.
The parotid gland sub-regional radiomics features correlate with earlier and more precise xerostomia predictions in patients undergoing treatment for head and neck cancer.

Epidemiological studies concerning the introduction of antipsychotic drugs for the elderly population who have had a stroke are restricted. To understand the prevalence, prescribing habits, and contributing factors behind antipsychotic use, we examined elderly stroke patients.
A retrospective cohort study was undertaken to pinpoint patients aged over 65 who were hospitalized for stroke using data extracted from the National Health Insurance Database (NHID). The discharge date was designated as the index date. The NHID database served as the source for estimating the incidence and prescription patterns of antipsychotic drugs. To research the elements influencing the introduction of antipsychotic medication, the cohort from the National Hospital Inpatient Database (NHID) was integrated with the data from the Multicenter Stroke Registry (MSR). Using the NHID, the study obtained data on demographics, comorbidities, and concurrent medications. Data points concerning smoking status, body mass index, stroke severity, and disability were extracted from the MSR through linking procedures. Post-index-date, the subject experienced the commencement of antipsychotic therapy, contributing to the outcome. Using the multivariable framework of the Cox model, hazard ratios for antipsychotic initiation were quantified.
Concerning the projected course of recovery, the two-month timeframe following a stroke displays the most elevated risk for the application of antipsychotic treatments. A significant risk of antipsychotic medication use was tied to the presence of multiple co-occurring diseases. In particular, chronic kidney disease (CKD) presented the strongest link, showing the highest adjusted hazard ratio (aHR=173; 95% CI 129-231) when compared with other factors influencing the risk. Concurrently, both the severity of the stroke and the associated disability were critical factors for the prescription of antipsychotic drugs.
The study found that elderly stroke patients grappling with chronic medical conditions, notably chronic kidney disease, alongside severe stroke severity and disability, experienced a greater risk of psychiatric disorders in the first two months after the stroke.
NA.
NA.

An assessment of the psychometric properties of self-management patient-reported outcome measures (PROMs) for chronic heart failure (CHF) patients is required.
From the earliest point in time up to June 1st, 2022, a search was carried out across eleven databases and two websites. find more Using the COSMIN risk of bias checklist, a consensus-based standard for the selection of health measurement instruments, the methodological quality was determined. Employing the COSMIN criteria, the psychometric properties of each PROM were evaluated and summarized. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, altered and enhanced, was applied to measure the reliability of the supporting evidence. Across 43 studies, the psychometric properties of 11 patient-reported outcome measures were assessed. The evaluation process consistently focused on the parameters of structural validity and internal consistency. The hypotheses testing of construct validity, reliability, criterion validity, and responsiveness lacked comprehensive coverage in the available data. NIR II FL bioimaging Regarding measurement error and cross-cultural validity/measurement invariance, no data were collected. High-quality evidence affirmed the psychometric characteristics of the Self-care of Heart Failure Index (SCHFI) v62, the SCHFI v72, and the European Heart Failure Self-care Behavior Scale 9-item (EHFScBS-9).
The conclusions drawn from SCHFI v62, SCHFI v72, and EHFScBS-9 research suggest the instruments' potential for evaluating self-management in CHF patients. A more thorough investigation of the psychometric properties, such as measurement error, cross-cultural validity, measurement invariance, responsiveness, and criterion validity, is required for a careful assessment of its content validity.
Reference code PROSPERO CRD42022322290 needs to be returned.
PROSPERO CRD42022322290, a scholarly endeavor of unparalleled importance, merits extensive analysis.

This study explores the diagnostic efficacy of radiologists and their radiology trainees when utilizing digital breast tomosynthesis (DBT) as the sole imaging technique.
The inclusion of synthesized views (SV) with DBT improves the understanding of DBT image adequacy in identifying cancer lesions.
Fifty-five observers (30 radiologists, 25 radiology trainees) assessed 35 cases, with 15 classified as cancer. Among the group of observers, 28 readers focused exclusively on Digital Breast Tomosynthesis (DBT), and 27 readers combined both DBT and Synthetic View (SV). For the task of mammogram interpretation, two reader groups encountered similar challenges. Percutaneous liver biopsy The ground truth served as the benchmark for evaluating the specificity, sensitivity, and ROC AUC of participant performances in each reading mode. Different breast densities, lesion types, and sizes were analyzed to determine the cancer detection rate variations between 'DBT' and 'DBT + SV' screening. To gauge the difference in diagnostic precision of readers operating under two distinct reading strategies, the Mann-Whitney U test was selected.
test.
The result, indicated by 005, was substantially meaningful.
Significant variability was not detected in the specificity measure, which was 0.67.
-065;
Sensitivity (077-069) stands out as a critical parameter.
-071;
ROC AUC results indicated 0.77 and 0.09.
-073;
A study assessing the difference in diagnostic performance between radiologists interpreting DBT with supplemental views (SV) and those interpreting DBT only. Equivalent outcomes were observed in radiology trainees, showing no substantial variation in specificity levels of 0.70.
-063;
Sensitivity (044-029) is a crucial element to understand in relation to other data points.
-055;
The ROC AUC values (0.59–0.60) were observed for a series of experiments.
-062;
The code 060 effectively separates two different reading modalities. In both reading modes, the cancer detection rate was similar for radiologists and trainees, regardless of the levels of breast density, cancer type, or the dimensions of lesions.
> 005).
The study's findings highlight the comparable diagnostic abilities of radiologists and radiology trainees in discerning cancerous and normal cases when utilizing digital breast tomosynthesis (DBT) alone or in conjunction with supplemental views (SV).
The diagnostic capabilities of DBT were equally effective as the combined use of DBT and SV, suggesting the possibility of DBT being implemented as the exclusive technique.
DBT demonstrated diagnostic accuracy comparable to the combined application of DBT and SV, potentially warranting its consideration as the sole imaging technique without SV.

While exposure to air pollution has been implicated in a higher risk of developing type 2 diabetes (T2D), studies investigating the differential susceptibility to air pollution's detrimental impacts among disadvantaged populations yield inconsistent results.
We investigated the variability in the relationship between air pollution and type 2 diabetes, taking into account sociodemographic factors, comorbid conditions, and concurrent exposures.
We quantified residential populations' exposure to
PM
25
An analysis of the air sample revealed the presence of ultrafine particles (UFP), elemental carbon, and further pollutants.
NO
2
Every resident of Denmark, during the period from 2005 to 2017, experienced the subsequent points. In summation,
18
million
In the key analytical group, individuals aged 50 to 80 years were included; within this group, 113,985 developed type 2 diabetes during the follow-up. Further research was done on
13
million
Ages ranging from 35 to 50 years. We assessed the relationship between five-year time-weighted running means of air pollution and T2D, stratified by sociodemographic characteristics, comorbidity, population density, road traffic noise, and green space proximity, using the Cox proportional hazards model (relative risk) and the Aalen additive hazard model (absolute risk).
A correlation exists between air pollution and type 2 diabetes, specifically pronounced among individuals aged 50 to 80 years of age, with a hazard ratio of 117 (95% confidence interval: 113-121).
5
g
/
m
3
PM
25
According to the findings, the estimate is 116, with a margin of error (95% confidence interval) of 113 to 119.
10000
UFP
/
cm
3
Air pollution's impact on type 2 diabetes was more pronounced among men than women in the 50-80 age group. This pattern persisted across socioeconomic factors, with those holding lower educational degrees showing a greater correlation compared to those with higher education. Similarly, individuals with a medium income level demonstrated stronger associations versus those with low or high income levels. Cohabitation also appeared linked to a stronger association than living alone. Finally, a higher correlation was observed in individuals with comorbidities in contrast to those without them.