Cemented or Uncemented Hemiarthroplasty for Intracapsular Hip Fracture.

BACKGROUND: Controversy exists over the use of bone cement in hip fractures treated with hemiarthroplasty. Only limited data on quality of life after cemented as compared with modern uncemented hemiarthroplasties are available. METHODS: We conducted a multicenter, randomized, controlled trial comparing cemented with uncemented hemiarthroplasty in patients 60 years of age or older with an intracapsular hip fracture. The primary outcome was health-related quality of life measured with the use of utility scores on the EuroQol Group 5-Dimension (EQ-5D) questionnaire at 4 months after randomization (range of scores, -0.594 to 1, with higher scores indicating better quality of life; range for minimal clinically important difference, 0.050 to 0.075). RESULTS: A total of 610 patients were assigned to undergo cemented hemiarthroplasty and 615 to undergo modern uncemented hemiarthroplasty; follow-up data were available for 71.6% of the patients at 4 months. The mean EQ-5D utility score was 0.371 in patients assigned to the cemented group and 0.315 in those assigned to the uncemented group (adjusted difference, 0.055; 95% confidence interval [CI], 0.009 to 0.101; P = 0.02). The between-group difference at 1 month was similar to that at 4 months, but the difference at 12 months was smaller than that at 4 months. Mortality at 12 months was 23.9% in the cemented group and 27.8% in the uncemented group (odds ratio for death, 0.80; 95% CI, 0.62 to 1.05). Periprosthetic fractures occurred in 0.5% and 2.1% of the patients in the respective groups (odds ratio [uncemented vs. cemented], 4.37; 95% CI, 1.19 to 24.00). The incidences of other complications were similar in the two groups. CONCLUSIONS: Among patients 60 years of age or older with an intracapsular hip fracture, cemented hemiarthroplasty resulted in a modestly but significantly better quality of life and a lower risk of periprosthetic fracture than uncemented hemiarthroplasty. (Funded by the National Institute for Health Research; WHiTE 5 ISRCTN number, ISRCTN18393176.).

The deltoid ligament complex is reliably visualised as four fascicles in two layers with 3D volumetric MRI in the ankles of 20 asymptomatic volunteers.

PURPOSE: The anatomy of the deltoid ligament is complex. There is agreement on the presence of superficial and deep layers but the number and frequency of fascicles remains controversial. Identifying injuries to specific components of the deltoid ligament may inform decision-making on their management. The anatomy was reviewed to establish the number and dimension of fascicles visible with three-dimensional (3D) volumetric magnetic resonance images (MRI). METHODS: Twenty ankles from asymptomatic healthy volunteers were imaged with 3D volumetric MRI. The presence of individual fascicles was recorded and measured in 3D. RESULTS: The median age of participants was 26 years (range: 20-37) of which 13 (65%) were female. All 20 ankles had a deltoid ligament formed of four fascicles in two layers: three fascicles in the superficial layer; tibionavicular (mean dimensions 22.5 × 10.0 × 2.4 mm), tibiospring (16.6 × 6.7 × 1.9 mm) and tibiocalcaneal (23.8 × 4.6 × 1.8 mm) and a deep layer consisting of the tibiotalar fascicle, which could be divided into two parts: anterior tibiotalar (mean dimensions 10 × 5.6 × 4.1 mm) and the significantly larger posterior tibiotalar (14.2 × 13.8 × 17.5 mm, p < 0.01). There were no additional fascicles observed. CONCLUSIONS: The deltoid ligament complex was consistently visualised as four fascicles (tibionavicular, tibiospring, tibiocalcaneal, tibiotalar) in two layers (superficial and deep) in all 20 ankles. The posterior part of the tibiotalar fascicle was the thickest of all the fascicles in the deltoid ligament. It is, therefore, possible to accurately identify the components of the deltoid ligament, and 3T MRI can be used to assess fascicle-specific injury, which will guide treatment and rehabilitation. LEVEL OF EVIDENCE: Level III.

Deltoid ligament injuries: A review of the anatomy, diagnosis and treatments.

PURPOSE: Ankle sprains remain the most common soft tissue injury presenting to Emergency Departments. Recently, there has been increased awareness and reporting of deltoid ligament injuries in association with injuries to the lateral ligament complex as well as with fibula fractures. This article reviews the currently available literature on the anatomy of the deltoid ligament, clinical and radiological diagnosis of injuries to the deltoid ligament and treatment recommendations. METHODS: A literature review was conducted for keywords associated with deltoid ligament injuries. MEDLINE, PubMed and Embase databases were utilised for this search. Articles were included if involving an adult population, were English-language, were related to deltoid ligament injuries (with or without associated injuries) and reported on patho-anatomy, clinical or radiological diagnosis or treatment methods. RESULTS: A total of 93 articles were assessed for relevance from the database search, and 47 were included after the removal of irrelevant articles and duplicates. Several studies reported on the clinical findings of deltoid ligament injury, as well as the radiographic analysis. Arthroscopy was considered the gold standard of diagnosis, with authors reporting on the potential benefit of performing arthroscopic repair or reconstruction at the same time. There were no studies that provided a system for the classification of deltoid ligament injury or larger studies of treatment pathways. Long-term studies of the incidence of instability in deltoid ligament injuries were not available. CONCLUSION: There is limited evidence available regarding deltoid ligament injuries, particularly in terms of treatment options, either in isolation or with concomitant injuries. Long-term follow-up studies are needed to obtain more accurate data on the number of complications. LEVEL OF EVIDENCE: Level IV.

The utility of plasma glycated CD59 in predicting postpartum glucose intolerance: A prospective study of women diagnosed with GDM during a period of universal GDM screening.

AIMS: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24-28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria. METHODS: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves. RESULTS: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70-0.91). A PP pGCD59 cut-off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9-100), specificity of 16.9% (95% CI: 9.8-26.3), positive predictive value of 22.1% (95% CI: 21.0-22.6), and negative predictive value of 100% (95% CI: 87.4-100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89-0.99) for the identification of PP glucose intolerance. CONCLUSION: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance.

Efforts to transfer ectopic embryos to the uterine cavity: A systematic review.

AIM: The objectives of this review are to identify and characterize attempts to transfer ectopic embryos to the uterus, and to understand arguments for and against the feasibility of such an intervention. METHODS: An electronic literature search involved all English language articles published in MEDLINE (1948-), Web of Science (1899-), and Scopus (1960-) before July 1, 2022. Articles were included that identify or describe attempts to transfer the embryo from its ectopic location to the uterine cavity, or discuss the feasibility of such an intervention; there were no exclusion criteria (PROSPERO registration number CRD42022364913). RESULTS: The initial search yielded 3060 articles; 8 articles were included. Of these, two articles were case reports that described the successful transfer of the embryo from its ectopic location to the uterus, followed by term births; both cases involved laparotomy with salpingostomy, followed by transfer of the embryonic sac into the uterine cavity through an opening made in the uterine wall. The other six articles varied in type, and provided a number of arguments for and against the feasibility of such a procedure. CONCLUSIONS: The evidence and arguments identified in this review may help manage expectations for those interested in transferring an ectopically implanted embryo in the hope of continuing the pregnancy, but who are uncertain about the extent to which such a procedure has been attempted or may be possible. Isolated case reports, with no evidence of replication, should be interpreted with the utmost caution and do not constitute a procedure for clinical use.

Introduction to computational causal inference using reproducible Stata, R, and Python code: A tutorial.

The main purpose of many medical studies is to estimate the effects of a treatment or exposure on an outcome. However, it is not always possible to randomize the study participants to a particular treatment, therefore observational study designs may be used. There are major challenges with observational studies; one of which is confounding. Controlling for confounding is commonly performed by direct adjustment of measured confounders; although, sometimes this approach is suboptimal due to modeling assumptions and misspecification. Recent advances in the field of causal inference have dealt with confounding by building on classical standardization methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where new estimators were developed to overcome the limitations of the previous estimators (ie, nonparametric and parametric g-formula, inverse probability weighting, double-robust, and data-adaptive estimators). We illustrate the implementation of different methods using an empirical example from the Connors study based on intensive care medicine, and most importantly, we provide reproducible and commented code in Stata, R, and Python for researchers to adapt in their own observational study. The code can be accessed at https://github.com/migariane/Tutorial_Computational_Causal_Inference_Estimators.

Order restricted inference in chronobiology.

This paper is motivated by applications in oscillatory systems where researchers are typically interested in discovering components of those systems that display rhythmic temporal patterns. The contributions of this paper are twofold. First, a methodology is developed based on a circular signal plus error model that is defined using order restrictions. This mathematical formulation of rhythmicity is simple, easily interpretable and very flexible, with the latter property derived from the nonparametric formulation of the signal. Second, we address various commonly encountered problems in the analysis of oscillatory systems data. Specifically, we propose a methodology for (a) detecting rhythmic signals in an oscillatory system and (b) estimating the unknown sampling time that occurs when tissues are obtained from subjects whose time of death is unknown. The proposed methodology is computationally efficient, outperforms the existing methods, and is broadly applicable to address a wide range of questions related to oscillatory systems.

Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

Order restricted inference for oscillatory systems for detecting rhythmic signals.

MOTIVATION: Many biological processes, such as cell cycle, circadian clock, menstrual cycles, are governed by oscillatory systems consisting of numerous components that exhibit rhythmic patterns over time. It is not always easy to identify such rhythmic components. For example, it is a challenging problem to identify circadian genes in a given tissue using time-course gene expression data. There is a great potential for misclassifying non-rhythmic as rhythmic genes and vice versa. This has been a problem of considerable interest in recent years. In this article we develop a constrained inference based methodology called Order Restricted Inference for Oscillatory Systems (ORIOS) to detect rhythmic signals. Instead of using mathematical functions (e.g. sinusoidal) to describe shape of rhythmic signals, ORIOS uses mathematical inequalities. Consequently, it is robust and not limited by the biologist's choice of the mathematical model. We studied the performance of ORIOS using simulated as well as real data obtained from mouse liver, pituitary gland and data from NIH3T3, U2OS cell lines. Our results suggest that, for a broad collection of patterns of gene expression, ORIOS has substantially higher power to detect true rhythmic genes in comparison to some popular methods, while also declaring substantially fewer non-rhythmic genes as rhythmic. AVAILABILITY AND IMPLEMENTATION: A user friendly code implemented in R language can be downloaded from http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/peddada/index.cfm CONTACT: peddada@niehs.nih.gov.

Mitral valve navigator. A new diagnostic tool for effective regurgitant orifice quantification in mitral regurgitation.

INTRODUCTION: Mitral regurgitation severity assessment is usually carried out using qualitative, semiquantitative, and quantitative parameters. The mitral valve navigation (MVN) tool allows to measure the mitral effective regurgitant orifice (MERO) from 3D echo datasets. Our aim was to validate the MVN as a new tool to quantify MERO. A secondary aim was to assess the intra- and interobserver variability. METHODS: This is a retrospective study in which consecutive subjects undergoing a transoesophageal echocardiogram for more than mild mitral regurgitation evaluation were included. MERO measurement obtained by means of 3D color Doppler was used as the gold standard method for comparison. In every patient, MERO was also obtained using the MVN tool. RESULTS: Fifty-nine consecutive patients were analyzed (47.5% female; mean age 50.8 years). Mitral regurgitation was moderate in 23 (39%) and severe in 36 (61%) patients. Forty patients (67.8%) had a primary and 19 (32.2%) a secondary mitral regurgitation. The intraclass correlation coefficient (ICC) between 3D color Doppler and MVN was excellent (ICC: 0.95; 95% CI: 0.82 to 0.98; P < 0.001) in the total group and for patients with primary and secondary mitral regurgitation. Intra- and interobserver agreements were also good. CONCLUSIONS: Mitral valve navigator shows an excellent accuracy for measuring MERO when the transoesophageal 3D color Doppler is used as the reference method, either primary or secondary mitral regurgitation. Intraobserver reproducibility and interobserver reproducibility are also excellent. These findings make this software a good alternative method to measure mitral regurgitation severity.

FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.

AIMS: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus. METHODS: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l-1 rivaroxaban. RESULTS: AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml-1  mg tissue-1 , P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87-74.03) pg ml-1  mg tissue-1 , P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control. CONCLUSIONS: FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

Circular piecewise regression with applications to cell-cycle data.

Applications of circular regression models appear in many different fields such as evolutionary psychology, motor behavior, biology, and, in particular, in the analysis of gene expressions in oscillatory systems. Specifically, for the gene expression problem, a researcher may be interested in modeling the relationship among the phases of cell-cycle genes in two species with differing periods. This challenging problem reduces to the problem of constructing a piecewise circular regression model and, with this objective in mind, we propose a flexible circular regression model which allows different parameter values depending on sectors along the circle. We give a detailed interpretation of the parameters in the model and provide maximum likelihood estimators. We also provide a model selection procedure based on the concept of generalized degrees of freedom. The model is then applied to the analysis of two different cell-cycle data sets and through these examples we highlight the power of our new methodology.

Utility of a mHealth App for Self-Management and Education of Cardiac Diseases in Spanish Urban and Rural Areas.

Analyze the utility of a mobile health app named HeartKeeper in several groups of population and obtain conclusions to be applied to other similar apps. A questionnaire has been designed to evaluate the usage and utility of the HeartKeeper app. The questionnaire information was collected by collaborating cardiologists from 32 patients before and after they used the app. Patients were randomly selected with established quotas within interest groups, so that men and women, patients older or younger than 60 years old and patients living in urban or rural areas were equally represented. Using the appropriate statistical techniques we see that the HeartKeeper app was useful for patients as they qualify with 70 points (out of 100) the overall opinion of the app, it helps them remember more easily taking their pills with a mean improvement of 20.94 points (p < 0.001) and they perceive a global improvement of their health (8.28 points, p < 0.001). We also observe that these improvements do not depend, in general, on the area (urban or rural) where the patient comes from or on their sex. Although older patients needed more help to use the app and used it slightly less frequently, the improvements on several measures considered, such as remembering taking pills, breathing problems or trouble developing activities, depend significantly (p < 0.05) on age with older patients reporting higher improvements than younger ones. The results obtained with the sample of patients considered in this research prove the utility of the HeartKeeper app. This utility is similar in urban and rural areas and for patients of both sexes and, to some extent, depends on the age of the patient with older patients reporting slightly lower frequency of use but higher health improvements than younger ones.

High-spatial-resolution bone densitometry with dual-energy X-ray absorptiometric region-free analysis.

PURPOSE: To outline the conceptual development of dual-energy absorptiometric (DXA) region-free analysis, quantify its precision, and evaluate its application to quantify the change in longitudinal femoral periprosthetic bone mineral density (BMD) in patients during the 12 months after total hip arthroplasty. MATERIALS AND METHODS: All subjects had undergone total hip arthroplasty for idiopathic arthritis, and the scans were collected as part of previous ethically approved studies (1998-2005) for which informed consent was provided. Contemporary image processing approaches were used to develop a region of interest-free DXA analysis method with increased spatial resolution for assessment of proximal femoral BMD. The method was calibrated, and its accuracy relative to a proprietary algorithm was assessed by using a hip phantom. The precision of the method was examined by using repeat DXA acquisitions in 29 patients, and its ability to allow spatial resolution of localized periprosthetic BMD change at the hip was assessed in an independent group of 19 patients who were measured throughout a 12-month period. Differences were evaluated with t tests (P < .05). RESULTS: The method allowed spatial resolution of more than 10 000 individual BMD data points on a typical archived prosthetic hip scan. The median data point-level error of the method after calibration was -1.9% (interquartile range, -7.2% to 3.5%) relative to a proprietary algorithm. The median data point-level precision, expressed as a coefficient of variation, was 1.4% (interquartile range, 1.2%-1.6%). Evaluation of BMD change in a model of periprosthetic bone loss demonstrated large but highly focal changes in BMD that would not be resolved by using traditional region of interest-based analysis approaches. CONCLUSION: The proposed approach provides a quantitative, precise method for extracting high-spatial-resolution BMD data from existing DXA datasets without the limitations imposed by region of interest-based analysis.

Thromboembolic risk in atrial fibrillation: association between left atrium mechanics and risk scores. A study based on 3D wall-motion tracking technology.

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a significantly high risk of stroke and systemic embolism. The aim of our study was to assess the association between left atrium (LA) mechanics measured by 3D wall-motion tracking (3DWMT) technology and the most common thromboembolic risk scores (CHADS2, CHA2DS2-VASc). METHODS: A total of 101 consecutive patients with permanent AF referred were included. Conventional bidimensional (2D) LA parameters, and LA mechanics by means of 3DWMT were studied. Association between LA 2D and 3DWMT parameters and both risk scores was evaluated as well as its correlation with every component of the score individually. RESULTS: Mean age was 78 ± 10 years. Mean CHADS2 was 2.7 ± 1.3 and mean CHA2DS2-VASc was 4.4 ± 1.7. Values of 2D and 3DWTM LA parameters were: 2D area 26.4 ± 9.7 cm(2) , 2D volume index 49.4 ± 10.1 mL/m(2) , 3DWMT left atrial emptying fraction (LAEF) 15.9 ± 8.4%, longitudinal strain 9.1 ± 4.5% and area strain 14.9 ± 8.8%. Linear regression analysis showed statistically significant correlation between LA longitudinal strain and LAEF with CHADS2 and CHA2DS2-VASc scores. For each 10% variation in longitudinal strain, CHADS2 and CHA2DS2-VASc scores change in 0.7 and 0.8 points, respectively. CONCLUSIONS: Left atrial longitudinal strain and emptying fraction assessed by 3D WMT technology have correlation with both CHADS2 and CHA2DS2-VASc scores. Each 10% of variation in longitudinal strain represents a 0.7 and 0.8 points change in those risk scores. LA mechanics evaluation might provide additional value to risk scores and could be considered to be a predictor of stroke in patients with AF.

Performance and estimation of the true error rate of classification rules built with additional information. An application to a cancer trial.

Classification rules that incorporate additional information usually present in discrimination problems are receiving certain attention during the last years as they perform better than the usual rules. Fernández, M. A., C. Rueda and B. Salvador (2006): "Incorporating additional information to normal linear discriminant rules," J. Am. Stat. Assoc., 101, 569-577, proved that these rules have lower total misclassification probability than the usual Fisher's rule. In this paper we consider two issues; on the one hand, we compare these rules with those based on shrinkage estimators of the mean proposed by Tong, T., L. Chen and H. Zhao (2012): "Improved mean estimation and its application to diagonal discriminant analysis," Bioinformatics, 28(4): 531-537. with regard to four criteria: total misclassification probability, area under ROC curve, well-calibratedness and refinement; on the other hand, we consider the estimation of the true error rate, which is a very interesting parameter in applications. We prove results on the apparent error rate of the rules that expose the need of new estimators of their true error rate. We propose four such new estimators. Two of them are defined incorporating the additional information into the leave-one-out-bootstrap. The other two are the corresponding cross-validation after bootstrap versions. We compare these estimators with the usual ones in a simulation study and in a cancer trial application, showing the good behavior of the rules that incorporate additional information and of the new leave-one-out bootstrap estimators of their true error rate.

Identification of a core set of signature cell cycle genes whose relative order of time to peak expression is conserved across species.

A cell division cycle is a well-coordinated process in eukaryotes with cell cycle genes exhibiting a periodic expression over time. There is considerable interest among cell biologists to determine genes that are periodic in multiple organisms and whether such genes are also evolutionarily conserved in their relative order of time to peak expression. Interestingly, periodicity is not well-conserved evolutionarily. A conservative estimate of a number of periodic genes common to fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae) ('core set FB') is 35, while those common to fission yeast and humans (Homo sapiens) ('core set FH') is 24. Using a novel statistical methodology, we discover that the relative order of peak expression is conserved in ∼80% of FB genes and in ∼40% of FH genes. We also discover that the order is evolutionarily conserved in six genes which are potentially the core set of signature cell cycle genes. These include ace2 (a transcription factor) and polo-kinase plo1, which are well-known hubs of early M-phase clusters, cdc18 a key component of pre-replication complexes, mik1 which is critical for the establishment and maintenance of DNA damage check point, and histones hhf1 and hta2.

isocir: An R Package for Constrained Inference using Isotonic Regression for Circular Data, with an Application to Cell Biology.

In many applications one may be interested in drawing inferences regarding the order of a collection of points on a unit circle. Due to the underlying geometry of the circle standard constrained inference procedures developed for Euclidean space data are not applicable. Recently, statistical inference for parameters under such order constraints on a unit circle was discussed in Rueda et al. (2009); Fernández et al. (2012). In this paper we introduce an R package called isocir which provides a set of functions that can be used for analyzing angular data subject to order constraints on a unit circle. Since this work is motivated by applications in cell biology, we illustrate the proposed package using a relevant cell cycle data.

COVID-19 Pandemic Control Measures and Their Impact on University Students and Family Members in a Central Region of Spain.

The first waves of the COVID-19 pandemic were times of great change in the lives of university students and their families in Spain. The aim of this study was to explore the psychosocial aspects and preventive measures carried out during the COVID-19 pandemic by students and family members of the nursing degree students of the University of Valladolid (Spain). The number of people surveyed was 877, by means of an ad hoc questionnaire. Relationships between variables were established by means of the Chi-square test and Student's t-test. In addition, multivariate logistic regression was generated. The significance level used was 0.05. Students and family members maintained preventive measures= such as hand washing, correct use of masks =in closed places, avoiding crowds and maintaining social distance, but at low rates (close to 20% in all cases). Regarding psychosocial aspects, 41.07% of the participants suffered from anxiety and loneliness, while 5.2% needed to take drugs to reduce anxiety or sleep and 66.07% were dependent on technology. Suicidal behavior is related to stress, anxiety, loneliness, poor family relationships, psychotropic drug use and technology abuse. The pandemic has caused life changes in university students and their families at the psychosocial level, generating high figures of suicidal ideation regardless of age. Preventive measures adopted to control the pandemic have not been followed for the most part.