bluuebunny/crossref_metadata_2025 huggingface dataset:
P484 Remote monitoring allows an individualized approach and showed excellent usability at the infusion unit
Authors: Fierens L , Geens P , De Dycker E , Paps A , Lambrechts T , Sabino J , Vermeire S , Ferrante M
Published: May 2021

Background

Given the high impact on health-related quality of life (HRQoL), IBD patients may benefit from continued monitoring by specialized caregivers. Patient-reported outcomes (PRO) can be collected through telemedicine in a reliable way, allowing to monitor patients even in between hospital visits and supporting patient-physician interaction. The aim of this study was to implement an electronic questionnaire into routine clinical practice and to explore its added value.

Methods

Since May 2020, all IBD patients visiting the infusion unit of our tertiary referral centre (+/- 130 patients/week) receive an electronic questionnaire one week prior to their visit. Questions about disease activity are included through the two-component PRO (PRO2), and about HRQoL in form of the IBD Disk, which visually shows the impact of disease on ten different health domains over time (lower scores seen in quiescent disease). Based on PRO2 scores, clinical remission was defined as a liquid stool frequency ≤1 and an abdominal pain score ≤1 in patients with Crohn’s disease (CD), and as a stool frequency score ≤1 and no rectal bleeding in patients with ulcerative colitis (UC). We evaluated PROs and participation rate, and the System Usability Scale (SUS) was used to evaluate usability of the new system.

Results

In Jan-Feb 2021, a total of 447 unique IBD patients completed the full questionnaire at least once [48.0% participation rate, 62.9% CD, 53.0% male, median age (IQR) 46.5 (33.8–56.8) years, 94,9% on biologic therapy, 61.5% in clinical remission, Figure 1]. No association was found between sex, age (group) or IBD type and adherence to the questionnaire. Median (IQR) IBD Disk scores were significantly lower for remitters versus non-remitters [11 (3–25) vs. 40 (21–59), p<0.001]. The most affected health dimension in all patients regardless of remission state was energy with differences for remitters [median (IQR) 2 (0–5)] and non-remitters [median (IQR) 6 (3–8)]. Whereas all ten health dimensions of the IBD Disk were highly correlated with disease activity (p<0.001, Figure 2), no correlation was found with disease type, sex, age (group) or type of biologic therapy. In Feb 2021, 375 patients of the same cohort were randomly invited to complete the SUS. A median (IQR) SUS score of 85 (71.25–91.25) was found, indicating excellent usability of the new system (n=113).

Conclusion

The results show high correlation between disease activity and the impact on HRQoL, especially energy levels. Based on these PROs a more individualized approach at the infusion unit could be installed. This system is currently also implemented for IBD patients who do not visit the infusion unit but receive oral or subcutaneous therapy or no maintenance therapy.
P491 Infectious risk of vedolizumab compared with other biological agents in the treatment of Inflammatory Bowel Disease
Authors: Innocenti T , Roselli J , Lynch E N , Apolito P , Parisio L , Bagnoli S , Macrì G , Rogai F , Milani S , Galli A , Milla M , Dragoni G
Published: May 2021

Background

Vedolizumab (VDZ) is a gut selective anti-α 4β 7 integrin antibody for the treatment of Inflammatory Bowel Disease with a well-known optimal safety profile. We aimed to compare the risk of infections of VDZ with that of anti-TNF drugs and ustekinumab, in patients with both ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

All CD and UC patients undergoing biological treatment at our centre between June 2013 and June 2020 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of exposure-adjusted infection rate of vedolizumab with that of anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs).

Results

The overall exposure-adjusted infection rate was 11.5/100 PYs. Detailed information about the infectious complications related to the different biologics is reported in Table 1. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations, and gut infections. The rate of serious infections was 1.3/100 PYs. Among the 85 patients who were on a VDZ therapy, 17 (3 CD and 14 UC, median age 64, IQR 31–68) suffered an infectious complication. The exposure-adjusted incidence rate for vedolizumab was 17.5/100 PYs, with CD patients having a lower infection risk compared with UC patients (p = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the VDZ group (p = 0.0001).

Conclusion

Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with UC have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this could be due to the gut-selective mechanism of action of vedolizumab.
P583 Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn’s disease: results from a large Italian cohort study
Authors: Mocci G , Cuomo A , Allegretta L , Aragona G , Colucci R , Della Valle N , Ferronato A , Forti G , Gaiani F , Graziani M G , Lorenzetti R , Luzza F , Penna A , Pica R , Piergallini S , Rodinò S , Scarcelli A , Zampaletta C , Cicerone C , Cocco A , De Angelis G , Donnarumma L , Pranzo G , Franceschi M , Gallina S , Grasso G , Larussa T , Luppino I , Faggiani R , Fanigliulo L , Pagnini C , Perazzo P , Sacco R , Sebkova L , Serio M E , De Monti A , Picchio M , Elisei W , Maconi G , Tursi A
Published: May 2021

Background

Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics

Methods

194 CD patients (108 males and 86 females, mean age 48 years (range 38–58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients

Results

At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up.

A logistic regression, UST therapy as thirdline therapy (after both anti-TNFα and vedolizumab), FC >200 μg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment

Conclusion

Ustekinumab seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.
P625 Characteristics of SARS-CoV-2 infection in IBD patients in the second and third wave compared with the first wave and with the data of general population
Authors: Guerra Marina I , Algaba A , Castro S , Jiménez L , Garza D , Aller M D M , Granja A , Guardiola A , Gil M , Ruiz P , Bermejo F
Published: May 2021

Background

Our aims were: 1.) to compare the characteristics of SARS-CoV-2 infection in IBD patients in the second and third wave with respect to the results published in our site in the first wave (I. Guerra et al. Inflamm Bowel Dis. 2021 Jan 1;27(1):25–33) and 2.) to compare the date of the second and third wave with data of general population from the Autonomous Community of Madrid

Methods

Cohort, observational study in IBD patients followed in our IBD Unit with SARS-CoV-2 infection between March 2020 and May 2020 (first wave) and between July 2020 to March 2021 (second-third wave). All data were collected by telephone interview and reviewing the electronical medical records

Results

The demographic characteristics of the patients included are shown in Table 1.

Regarding clinical features of SARS-CoV-2 infection in both group of patients are represented in Table 2.

The severity of disease was not related to immunomodulators and/or biological treatments in both cohorts.

The number of COVID-19 cases by date in our IBD Unit in comparison with the cases in the Community of Madrid are shown in the Figure 1.

Conclusion

The patients diagnosed in the first wave were older and more symptomatic. Although the number of severe cases was higher in the first wave, influenced by the limited availability of tests in that period, no difference was found in mortality or in the percentage of ICU admissions.Severity of SARS-CoV-2 infection was not related to immunosuppression and in the second-third wave the IBD treatment was maintained more frequently.The distribution of cases in our series was in concordance with the data obtained in the general population.
P674 Definition of a microbial signature as a predictor of anti-TNFα treatment response
Authors: Oliver L , Busquets D , Amoedo J , Ramió-Pujol S , Malagón M , Serrano M , Bahí A , Lluansí A , Gilabert P , Miquel-Cusachs J O , Sàbat M , Guardiola J , Serra-Pagès M , Garcia-Gil J , Aldeguer X
Published: May 2021

Background

Crohn’s disease (CD) and ulcerative colitis (UC) evolve with alternate outbreaks and remissions of variable duration. Tumour necrosis factor α antagonists (anti-TNFα) have enhanced the treatment of patients with inflammatory bowel disease (IBD), improving the patient’s quality of life by reducing the number of surgeries and hospitalizations. Despite these advances, about 10–30% of patients do not respond to the treatment after the induction period.

Recent studies have pointed, on one hand, gut microbiota can play a role in the anti-TNFα treatment response as gram-positive bacteria can modulate the response of NOD proteins and, on the other hand, gram-negative bacteria can stimulate TLR4 receptors causing activation of NFkß.

This study aimed to define a microbial signature that could be used to predict the response of patients with CD and UC to anti-TNFα treatment.

Methods

This observational study consisted of obtaining a stool sample from 38 IBD patients before starting an anti-TNFα treatment. Patients were recruited at Hospital Universitari Dr. Josep Trueta (Girona) and Hospital Universitari de Bellvitge (l’Hospitalet de Llobregat).

During the one-year follow-up period, disease activity levels, faecal calprotectin evolution, and anti-TNFα antibody levels were analysed to assess response to treatment, differentiating 2 groups: responders and non-responders.

From each sample, DNA was purified and used in a qPCR for the quantification of the following markers: F. prausnitzii (Fpra) and its phylogroups (PHG-I and PHG-II), E. coli (Eco), A. muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac), M. smithii (Msm), and the total bacterial load (Eub).

Results

In this proof of concept, the predictive ability to identify anti-TNFα treatment responders was analysed. Individually, none of biomarkers demonstrated the ability to differentiate between groups with high sensitivity and specificity. However, an algorithm consisting of the combination of 5 microbial markers (Msm, Fpra, PHGII, Rum, and Eub) showed a high capacity to discriminate between responders and non-responders. The algorithm proved high sensitivity and specificity reporting values ​​of 93.33% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment.

Conclusion

A specific microbial signature could beneficiate patients with IBD by predicting the therapeutic effectiveness of an anti-TNFα treatment, which could lead to a personalized therapy, improving the patients’ quality of life, saving costs, and gaining time in patient recovery.A larger prospective study will be needed to validate these results.
P502 Dietary habits and nutritional status in children and adolescents with Inflammatory Bowel Disease: an italian multicenter case-control study (NUTRIBD study)
Authors: Gatti S , Vallorani M , Zoppi E , Aloi M , Bramuzzo M , Felici E , Panceri R , Ciacchini B , Catassi G , Grazian F , Catassi C
Published: May 2021

Background

Nutrition is involved in several aspects of pediatric IBD, ranging from disease etiology to induction and maintenance of disease. Presence of nutritional deficiencies can influence clinical outcomes and affect the immune system, growth and sexual maturation in children. Few studies assessed the dietary intake of IBD’s pediatric patients and investigated whether their dietary intakes meet the recommended daily allowances (RDA).

Methods

Children and adolescents with a diagnosis of IBD (> 1 year) and healthy controls (age and gender matched) were prospectively enrolled in 5 pediatric Italian IBD units. Daily dietary intake in the previous 6 months was assessed using a Food Frequency Questionnaire (FFQ). Energy intake (EI) and macro and micronutrients intakes were compared to the national RDA (LARN) and EI to the predicted total energy expenditure (TEE) based on the Schofield equation. Adherence to the Mediterranean diet was measured through the KIDMED score. Clinical and auxological data were recorded

Results

110 IBD subjects and 110 controls (median age±SD: 14,6 ±2,2 and 13,8±2,8 years, p= 0,45) were enrolled. Weight and height z-scores were significantly lower in IBD compared to controls (p= 0,0005 and p=0,036).Weight, height and BMI z-score did not differ between CD and UC. EI (Kcal/day), the EI/RDA ratio (%) and the EI/TEE ratio (%) were significantly lower in IBD compared to the controls (1893 vs 2068 kcal/day, p= 0,009; 71,5% vs 84,7%, p< 0,0001; 79,8% vs 90,8%, p=0,007). When distributing patients by clinical disease activity, the TEE was lower in patients with active disease compared to patients in remission (1850 vs 1915; p=0,039). A significant correlation was not found between age, gender, type of disease, disease activity, and EI/RDA % and EI/TEE %. Total protein and fat intake were lower in children with IBD compared to controls. Conversely the total carbohydrate intake did not differ between IBD patients and controls (median 289,8 vs 311,7 gr/day, p= 0,077) while the percentage of carbohydrate to EI was higher (CHO % : 61 vs 58; p=0,012). Total charbohydrates intake was significantly lower in patients with active disease compared to patients in remission (265.7 vs 294.3 gr/day; p=0,002). IBD patients reported a lower intake of the main dietary micronutrients compared to controls. A poor adherence to the Mediterranean diet was more frequent in IBD children (37.2% vs 22.7%, p= 0,013).

Conclusion

The diet of Italian children and adolescents with IBD differs substantially from the general pediatric population and frequently does not meet the RDA. Our data suggest the need of an accurate evaluation of the dietary intake and nutritional status in order to prevent nutritional deficiencies and promote health.
Coffee price dynamics: an analysis of the retail-international price margin
Authors: Ghoshray Atanu , Mohan Sushil
Published: May 2021

We examine the dynamics of the margin between retail and international coffee prices from 1980 to 2018. We find no significant trend in the margin using a robust procedure for estimating a trend. Further, we establish that any deviations in the margin are transitory for the full sample as well as the periods prior to and after the demise of the ICA, but with asymmetric adjustment. One of the reasons for the observed asymmetry could be market concentration in the coffee supply chain at the coffee roasting level, which allows coffee roasters to keep a higher share of the profits.
Long Term Prognostic Impact of Sex-specific Longitudinal Changes in Blood Pressure. The EPIC-Norfolk Prospective Population Cohort Study
Authors: Pana Tiberiu A , Luben Robert N , Mamas Mamas A , Potter John F , Wareham Nicholas J , Khaw Kay-Tee , Myint Phyo K
Published: May 2021

Aims

We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age.

Methods and results

Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies.

Conclusion

We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure.
Are Geckos Special in Sex Determination? Independently Evolved Differentiated ZZ/ZW Sex Chromosomes in Carphodactylid Geckos
Authors: Augstenová Barbora , Pensabene Eleonora , Veselý Milan , Kratochvíl Lukáš , Rovatsos Michail
Published: May 2021

Amniotes possess astonishing variability in sex determination ranging from environmental sex determination (ESD) to genotypic sex determination (GSD) with highly differentiated sex chromosomes. Geckos are one of the few amniote groups with substantial variability in sex determination. What makes them special in this respect? We hypothesized that the extraordinary variability of sex determination in geckos can be explained by two alternatives: 1) unusual lability of sex determination, predicting that the current GSD systems were recently formed and are prone to turnovers; and 2) independent transitions from the ancestral ESD to later stable GSD, which assumes that geckos possessed ancestrally ESD, but once sex chromosomes emerged, they remain stable in the long term. Here, based on genomic data, we document that the differentiated ZZ/ZW sex chromosomes evolved within carphodactylid geckos independently from other gekkotan lineages and remained stable in the genera Nephrurus, Underwoodisaurus, and Saltuarius for at least 15 Myr and potentially up to 45 Myr. These results together with evidence for the stability of sex chromosomes in other gekkotan lineages support more our second hypothesis suggesting that geckos do not dramatically differ from the evolutionary transitions in sex determination observed in the majority of the amniote lineages.
Skin Tone and Perceived Discrimination: Health and Aging Beyond the Binary in NSHAP 2015
Authors: Monk Ellis P , Kaufman Jerry , Montoya Yadira
Published: May 2021

Objectives

This paper introduces new measures of skin tone (self-reported) and perceived discrimination that are included in the third round of the National Social Life, Health, and Aging Project (NSHAP). We explain the rationale for these new measures, emphasizing, in particular, how they help researchers to conceptualize and measure the significance of race/ethnicity for health and aging beyond binary ethnoracial categories.

Method

We describe new measures of skin tone and perceived discrimination for use in NSHAP 2015. We provide descriptive statistics on the distribution of skin tone (self-reported) by race/ethnicity. As a proof of concept, we use logistic and ordinary least squares regression analyses to examine the relationship between skin tone, perceived discrimination, and perceived stress among ethnoracial minorities.

Results

We find that there is significant variation in skin tone among non-White respondents in NSHAP 2015 (e.g., non-Hispanic Black and Latinx). We also find that skin tone (self-reported) is a significant predictor of the frequency of perceived discrimination and perceived stress among African American, but not Latinx respondents in NSHAP.

Discussion

The inclusion of new skin tone and discrimination measures in NSHAP 2015 provides a unique and novel opportunity for researchers to more deeply understand how race/ethnicity is connected to health and aging among ethnoracial minorities. Furthermore, it will enable analyses of how stress and perceived discrimination also affect patterns of health and aging among Whites against the backdrop of steadily increasing socioeconomic inequalities and shifting ethnoracial demographics in the United States.
A modified specific barrier model based on new time functions and approach for cracks location on the fault plane: application to the 2008 Iwate–Miyagi earthquake
Authors: Rezaei Mohammad Hadi , Khaji Naser , Di Maio Rosa , Emolo Antonio
Published: May 2021

Specific barrier method (SBM) is a method used for ground motion generation from a finite fault surface. It is based on a regular distribution of rupturing circular subevents located on the fault plane and random arrival times of the waves generated by those cracks. This approach does not consider the whole rupture kinematics, that is the rupture propagation from the hypocentre to the subevents, and leaves parts of the fault unbroken (barriers). In this paper, we propose a modified version of the SBM for generation of synthetic ground motions from a fault surface. In this version, we modify the probability density function (PDF) for the arrival time of the waves coming from different parts of the fault in order to better account for the fault kinematics and the distance between fault point and receiver. In this way, we can simulate the middle part of the acceleration spectrum (i.e. between 0.1 and 7 Hz) with more accuracy. Moreover, a new arrangement for locating cracks throughout the fault plane is proposed to add flexibility to the model and enable it to make the part of the spectrum with frequency larger than 7 Hz more like what happens in nature. In such an arrangement, called geometry packing in this paper, the size of circles varies within a chosen specific allowable range, while the circles cover all over the fault plane without any overlaps. To validate the proposed modified SBM technique, the synthetic Fourier spectra are compared with recordings of the 2008 Mw6.9 Iwate–Miyagi (Japan) earthquake. Finally, we present some parametric studies to show how different features of the proposed PDFs affect the results from the SBM approach.
Cognitive deficits in episodic ataxia type 2 mouse models
Authors: Bohne Pauline , Mourabit Damian Boden-El , Josten Mareike , Mark Melanie D
Published: May 2021

Episodic ataxia type 2 (EA2) is a rare autosomal dominant disorder characterized by motor incoordination, paroxysmal dystonia, vertigo, nystagmus and more recently cognitive deficits. To date over 100 mutations in the CACNA1A gene have been identified in EA2 patients leading to a loss of P/Q-type channel activity, dysfunction of cerebellar Purkinje cells and motor incoordination. To determine if the cerebellum is contributing to these cognitive deficits, we examined two different EA2 mouse models for cognition impairments where CACNA1A was removed specifically from cerebellar Purkinje or granule cells postnatally. Both mutant mouse models showed anxiolytic behavior to lighted, open areas in the open field and light/dark place preference tests but enhanced anxiousness in the novel suppressed feeding test. However, EA2 mice continued to show augmented latencies in the light/dark preference test and when the arena was divided into two dark zones in the dark/dark preference test. Moreover, increased latencies were also displayed in the novel object recognition test, indicating that EA2 mice are indecisive and anxious to explore new territories and objects and may have memory recognition deficits. Exposure to a foreign mouse led to deficiencies in attention and sniffing as well as in social and genital sniffing. These data suggest that postnatal removal of the P/Q type calcium channel from the cerebellum regulates neuronal activity involved in anxiety, memory, decision making and social interactions. Our EA2 mice will provide a model to identify the mechanisms and therapeutic agents underlying cognitive and psychiatric disorders seen in EA2 patients.
Agreement between pharmaceutical claims data and patient-reported medication use after stroke
Authors: Dalli Lachlan L , Andrew Nadine E , Cadilhac Dominique A , Kim Joosup , Sanfilippo Frank M , Kilkenny Monique F
Published: May 2021

Objectives

To assess the agreement between pharmaceutical claims data and patient-reported medication use after stroke.

Methods

Claims data from the Pharmaceutical Benefits Scheme were used to estimate medication use for a subset of participants registered in the Australian Stroke Clinical Registry in 2016. Estimates on medication use were validated against patient-reported responses (considered the reference standard).

Key findings

For antihypertensive and lipid-lowering medications, the sensitivity of claims data was excellent (85–87%) and the specificity was good (73–78%). Whereas for antithrombotic medications, sensitivity was modest (61%), but specificity was excellent (85%).

Conclusions

Pharmaceutical claims data can be used to infer medication use after stroke with mostly good to excellent sensitivity and specificity compared with the patient report.
Diagnostic Performance of Contrast-enhanced Mammography: Comparison With MRI and Mammography
Authors: Yüzkan Sabahattin , Cengiz Duygu , Hekimsoy İlhan , Sezgin Okçu Özlem , Oktay Ayşenur
Published: May 2021

Objective

To compare the diagnostic performance of contrast-enhanced mammography (CEM) with MRI and mammography (MG) based on histopathological results.

Methods

In this IRB-approved study, written informed consent was obtained from all patients. Images from 40 patients (62 lesions) with suspicious findings on US between March 2018 and August 2018 were evaluated. Sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CEM, MRI, and MG were evaluated and compared within a 95% confidence interval. Maximum dimensions of lesions were measured and correlations of results were evaluated with Spearman’s Rho test.

Results

In the histopathological analysis, 66% (41/62) of lesions were malignant and 34% (21/62) of lesions were benign. Contrast-enhanced mammography, MRI, and MG had sensitivities of 100% (41/41), 100% (41/41), and 80% (33/41), respectively. The sensitivity of CEM and MRI was significantly better than that of MG (P = 0.03). The NPVs of CEM (100%, 7/7) and MRI (100%, 14/14) were statistically higher than the NPV of MG (60%, 12/20) (P = 0.03). The false-positive rates for CEM, MRI, and MG were 33% (7/21), 66% (14/21), and 42% (9/21), respectively. Contrast-enhanced mammography had a significantly lower false-positive rate than MRI (P < 0.001). Mammography had the highest false-negative rate, missing 19% (8/41) of malignant lesions.

Conclusion

Contrast-enhanced mammography has similar performance characteristics to MRI and improved performance characteristics relative to MG. In particular, CEM and MRI have similar sensitivity and NPVs and both are superior in each of these metrics to MG.
Torture by Non-state Actors
Authors: Le Moli Ginevra
Published: May 2021

In legal discourse, ‘torture’ is a term used to describe the deliberate infliction of severe physical or mental pain and suffering upon a person. One controversial aspect of the legal definition of torture has been the status of the perpetrator, whose acts are relevant for the purposes of the torture definition under international law. This ambiguity came to the forefront in the judgment of the United Kingdom (UK) Supreme Court in R v. Reeves Taylor, where the Court ruled that the category of persons ‘acting in an official capacity’ (under section 134 of the Criminal Justice Act 1988, which implements the United Nations Convention against Torture) included members of armed groups, if those groups exercise governmental authority over a civilian population in a territory under their control. This article relies on R v. Reeves Taylor as a gateway for a wider analysis of four fundamental inquiries into the definition and operation of the crime of torture: (i) the rationales underlying the international criminal repression of torture; (ii) the rules (including the UN Convention as well as other rules) which give expression to different rationales; (iii) the spectrum of actors whose acts can constitute torture under different rationales and rules; and (iv) the wider implications of expanding the spectrum of possible perpetrators.
Constraining black hole feedback in galaxy clusters from X-ray power spectra
Authors: Heinrich Annie , Chen Yi-Hao , Heinz Sebastian , Zhuravleva Irina , Churazov Eugene
Published: May 2021

Jets launched by the supermassive black holes in the centres of cool-core clusters are the most likely heat source to solve the cooling flow problem. One way for this heating to occur is through generation of a turbulent cascade by jet-inflated bubbles. Measurements of the X-ray intensity power spectra show evidence of this cascade in different regions of the cluster, constraining the role of driving mechanisms. We analyse feedback simulations of the Perseus cluster to constrain the effect of the jet activity on the intensity fluctuations and kinematics of the cluster atmosphere. We find that, within the inner 60 kpc, the power spectra of the predicted surface brightness fluctuations are broadly consistent with those measured by Chandra and that even a single episode of jet activity can generate a long-lasting imprint on the intensity fluctuations in the innermost region of the cluster. Active galactic nucleus (AGN)-driven motions within the same region approach the values reported by Hitomi during and right after the AGN episode. However, the line-of-sight velocity dispersion excited by the jet in simulations underpredicts the Hitomi measurement. This indicates that driving a volume-filling sustained level of turbulence requires several episodes of jet activity, and/or additional processes drive turbulence outside the 60-kpc sphere. This also suggests that sharp edges of the bubbles in the innermost region of the cluster contribute substantially to the intensity of fluctuations, consistent with the Perseus observations in the inner 30-kpc region. We discuss new diagnostics to decompose annular power spectra to constrain past episodes of jet activity.
Binary black hole mergers from hierarchical triples in open clusters
Authors: Britt Dylan , Johanson Ben , Wood Logan , Miller M Coleman , Michaely Erez
Published: May 2021

A promising channel for producing binary black hole mergers is the Lidov–Kozai orbital resonance in hierarchical triple systems. While this mechanism has been studied in isolation, the distribution of such mergers in time and across star-forming environments is not well characterized. In this work, we explore Lidov–Kozai-induced black hole mergers in open clusters, combining semi-analytical and Monte Carlo methods to calculate merger rates and delay times for nine different population models. We predict a merger rate density of ∼1–10 Gpc−3 yr−1 for the Lidov–Kozai channel in the local Universe, and all models yield delay-time distributions in which a significant fraction of binary black hole mergers (e.g. ∼20–50 per cent in our baseline model) occur during the open cluster phase. Our findings suggest that a substantial fraction of mergers from hierarchical triples occur within star-forming regions in spiral galaxies.
The galaxy size–halo mass scaling relations and clustering properties of central and satellite galaxies
Authors: Rodriguez Facundo , Montero-Dorta Antonio D , Angulo Raul E , Artale M Celeste , Merchán Manuel
Published: May 2021

In this work, we combine size and stellar mass measurements from the Sloan Digital Sky Server (SDSS) with the group finder algorithm of Rodriguez & Merchán in order to determine the stellar and halo mass–size relations of central and satellite galaxies separately. We show that, while central and satellite galaxies display similar stellar mass–size relations, their halo mass–size relations differ significantly. As expected, more massive haloes tend to host larger central galaxies. However, the size of satellite galaxies depends only slightly on halo virial mass. We show that these results are compatible with a remarkably simple model in which the size of central and satellite galaxies scales as the cubic root of their host halo mass, with the normalization for satellites being ∼30  per cent smaller than that for central galaxies, which can be attributed to tidal stripping. We further check that our measurements are in excellent agreement with predictions from the IllustrisTNG hydrodynamical simulation. In the second part of this paper, we analyse how the clustering properties of central and satellite galaxies depend on their size. We demonstrate that, independently of the stellar mass threshold adopted, smaller galaxies are more tightly clustered than larger galaxies when either the entire sample or only satellites are considered. The opposite trend is observed on large scales when the size split is performed for the central galaxies alone. Our results place significant constraints for halo–galaxy connection models that link galaxy size with the properties of their hosting haloes.
A long-term multifrequency study of solar rotation using the solar radio flux and its relationship with solar cycles
Authors: Singh Vivek Kumar , Chandra Satish , Thomas Sanish , Sharma Som Kumar , Vats Hari Om
Published: May 2021

This paper examines long-term (more than four solar cycles) temporal and spatial fluctuations in the solar rotation by investigating radio-emission escapes from various layers of the solar atmosphere during the years 1967–2010. The flux modulation approach can also be used to investigate variations in solar rotation, which is a contentious topic in solar physics. This study makes use of a time-series of radio flux data at various frequencies (245–15 400 MHz) obtained at Sagamore Hill Solar Radio Observatory in Massachusetts, USA, and at other observatories from 1967 to 2010. The periodicity present in the temporal variation of the time-series is estimated through a Lomb–Scargle periodogram. The rotation period estimated for five radio emissions (606, 1415, and 2695 MHz from the corona, and 4995 and 8800 MHz from the transition region) through a statistical approach shows continuous temporal and spatial variations throughout the years. The smoothed rotation period shows the presence of periodic ∼22-yr and ∼11-yr components. The 22-yr component could be linked to the reversal of the solar magnetic field (Hale) cycle, while the 11-yr component is most likely related to the sunspot (Schwabe) cycle. In addition to these two components, random components are also prominently present in the analysed data. The cross-correlation between the sunspot number and the rotation period obtained shows a strong correlation with the 11-yr Schwabe and 22-yr Hale cycle. The corona rotates faster or slower than the transition region in different epochs. The alternation of the faster rotation speed between the corona and transition region also follows the 22-yr cycle.
Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor
Authors: Pajak Joshua , Dill Erik , Reyes-Aldrete Emilio , White Mark A , Kelch Brian A , Jardine Paul J , Arya Gaurav , Morais Marc C
Published: May 2021

Double-stranded DNA viruses package their genomes into pre-assembled capsids using virally-encoded ASCE ATPase ring motors. We present the first atomic-resolution crystal structure of a multimeric ring form of a viral dsDNA packaging motor, the ATPase of the asccφ28 phage, and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Based on these results, and previous single-molecule data and cryo-EM reconstruction of the homologous φ29 motor, we propose an overall packaging model that is driven by helical-to-planar transitions of the ring motor. These transitions are coordinated by inter-subunit interactions that regulate catalytic and force-generating events. Stepwise ATP binding to individual subunits increase their affinity for the helical DNA phosphate backbone, resulting in distortion away from the planar ring towards a helical configuration, inducing mechanical strain. Subsequent sequential hydrolysis events alleviate the accumulated mechanical strain, allowing a stepwise return of the motor to the planar conformation, translocating DNA in the process. This type of helical-to-planar mechanism could serve as a general framework for ring ATPases.
sRNA-mediated RNA processing regulates bacterial cell division
Authors: Grützner Julian , Remes Bernhard , Eisenhardt Katrin M H , Scheller Daniel , Kretz Jonas , Madhugiri Ramakanth , McIntosh Matthew , Klug Gabriele
Published: May 2021

Tight control of cell division is essential for survival of most organisms. For prokaryotes, the regulatory mechanisms involved in the control of cell division are mostly unknown. We show that the small non-coding sRNA StsR has an important role in controlling cell division and growth in the alpha-proteobacterium Rhodobacter sphaeroides. StsR is strongly induced by stress conditions and in stationary phase by the alternative sigma factors RpoHI/HII, thereby providing a regulatory link between cell division and environmental cues. Compared to the wild type, a mutant lacking StsR enters stationary phase later and more rapidly resumes growth after stationary phase. A target of StsR is UpsM, the most abundant sRNA in the exponential phase. It is derived from partial transcriptional termination within the 5′ untranslated region of the mRNA of the division and cell wall (dcw) gene cluster. StsR binds to UpsM as well as to the 5′ UTR of the dcw mRNA and the sRNA-sRNA and sRNA-mRNA interactions lead to a conformational change that triggers cleavage by the ribonuclease RNase E, affecting the level of dcw mRNAs and limiting growth. These findings provide interesting new insights into the role of sRNA-mediated regulation of cell division during the adaptation to environmental changes.
Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers’ Diarrhea
Authors: Johnson Ryan C , Van Nostrand Joy D , Tisdale Michele , Swierczewski Brett , Simons Mark P , Connor Patrick , Fraser Jamie , Melton-Celsa Angela R , Tribble David R , Riddle Mark S
Published: May 2021

Background

Travelers’ diarrhea (TD) is common among military personnel deployed to tropical and subtropical regions. It remains unclear how TD and subsequent antibiotic treatment impact the resident microflora within the gut, especially given increased prevalence of antibiotic resistance among enteric pathogens and acquisition of multidrug-resistant organisms. We examined functional properties of the fecal microflora in response to TD, along with subsequent antibiotic treatment.

Methods

Fecal samples from US and UK military service members deployed to Djibouti, Kenya, and Honduras who presented with acute watery diarrhea were collected. A sample was collected at acute presentation to the clinic (day 0, before antibiotics), as well as 7 and/or 21 days following a single dose of antibiotics (azithromycin [500 mg], levofloxacin [500 mg], or rifaximin [1650 mg], all with loperamide). Each stool sample underwent culture and TaqMan reverse transcription polymerase chain reaction analyses for pathogen and antibiotic resistance gene detection. Purified DNA from each sample was analyzed using the HumiChip3.1 functional gene array.

Results

In total, 108 day 1 samples, 50 day 7 samples, and 94 day 21 samples were available for analysis from 119 subjects. Geographic location and disease severity were associated with distinct functional compositions of fecal samples. There were no overt functional differences between pre- and postantibiotic treatment samples, nor was there increased acquisition of antibiotic resistance determinants for any of the antibiotic regimens.

Conclusions

These results indicate that single-dose antibiotic regimens may not drastically alter the functional or antibiotic resistance composition of fecal microflora, which should inform clinical practice guidelines and antimicrobial stewardship.

Clinical Trials Registration Number

NCT01618591.
The Generation of Arc Andesites and Dacites in the Lower Crust of a Cordilleran Arc, Fiordland, New Zealand
Authors: Carty Kendra , Schwartz Joshua J , Wiesenfeld John , Klepeis Keith A , Stowell Harold H , Tulloch Andy J , Barnes Calvin G
Published: May 2021

We present microbeam major- and trace-element data from 14 monzodiorites collected from the Malaspina Pluton (Fiordland, New Zealand) with the goal of evaluating processes involved in the production of andesites in lower arc crust. We focus on relict igneous assemblages consisting of plagioclase and amphibole with lesser amounts of clinopyroxene, orthopyroxene, biotite and quartz. These relict igneous assemblages are heterogeneously preserved in the lower crust within sheeted intrusions that display hypersolidus fabrics defined by alignment of unstrained plagioclase and amphibole. Trace-element data from relict igneous amphiboles in these rocks reveal two distinct groups: one relatively enriched in high field strength element concentrations and one relatively depleted. The enriched amphibole group has Zr values in the range of ∼25–110 ppm, Nb values of ∼5–32 ppm, and Th values up to 2·4 ppm. The depleted group, in contrast, shows Zr values <35 ppm and Nb values <0·25 ppm, and Th is generally below the level of detection. Amphibole crystallization temperatures calculated from major elements range from ∼960 to 830 °C for all samples in the pluton; however, we do not observe significant differences in the range of crystallization temperatures between enriched (∼960–840 °C) and depleted groups (∼940–830 °C). Bulk-rock Sr and Nd isotopes are also remarkably homogeneous and show no apparent difference between enriched (εNdi = 0·1 to –0·1; 87Sr/86Sri = 0·70420–0·70413) and depleted groups (εNdi = 0·3 to –0·4; 87Sr/86Sri = 0·70424–0·70411). Calculated amphibole-equilibrium melt compositions using chemometric equations indicate that melts were highly fractionated (molar Mg# <50), andesitic to dacitic in composition, and were much more evolved than bulk lower continental crust or primitive basalts and andesites predicted to have formed from hydrous melting of mantle-wedge peridotite beneath an arc. We suggest that melts originated from a common, isotopically homogeneous source beneath the Malaspina Pluton, and differences between enriched and depleted trace-element groups reflect varying contributions from subducted sediment-derived melt and sediment-derived fluid, respectively. Our data demonstrate that andesites and dacites were the dominant melts that intruded the lower crust, and their compositions mirror middle and upper bulk-continental crust estimates. Continental crust-like geochemical signatures were acquired in the source region from interaction between hydrous mantle-wedge melts and recycled subducted sediment rather than assimilation and/or remelting of pre-existing lower continental crust.
Trade-offs between risks of predation and starvation in larvae make the shelf break an optimal spawning location for Atlantic bluefin tuna
Authors: Shropshire Taylor A , Morey Steven L , Chassignet Eric P , Karnauskas Mandy , Coles Victoria J , Malca Estrella , Laiz-Carrión Raúl , Fiksen Øyvind , Reglero Patricia , Shiroza Akihiro , Quintanilla Hervas José M , Gerard Trika , Lamkin John T , Stukel Michael R
Published: May 2021

Atlantic bluefin tuna (ABT) (Thunnus thynnus) travel long distances to spawn in oligotrophic regions of the Gulf of Mexico (GoM) which suggests these regions offer some unique benefit to offspring survival. To better understand how larval survival varies within the GoM a spatially explicit, Lagrangian, individual-based model was developed that simulates dispersal and mortality of ABT early life stages within realistic predator and prey fields during the spawning periods from 1993 to 2012. The model estimates that starvation is the largest cumulative source of mortality associated with an early critical period. However, elevated predation on older larvae is identified as the main factor limiting survival to late postflexion. As a result, first-feeding larvae have higher survival on the shelf where food is abundant, whereas older larvae have higher survival in the open ocean with fewer predators, making the shelf break an optimal spawning area. The modeling framework developed in this study explicitly simulates both physical and biological factors that impact larval survival and hence could be used to support ecosystem based management efforts for ABT under current and future climate conditions.
Bound states of the Yukawa potential from hidden supersymmetry
Authors: Napsuciale M , Rodríguez S
Published: May 2021

We present a phenomenological study of the complete analytical solution to the bound eigenstates and eigenvalues of the Yukawa potential obtained previously using the hidden supersymmetry of the system and a systematic expansion of the Yukawa potential in terms of $\delta=a_{0}/D$, where $a_{0}$ is the Bohr radius and $D$ is the screening length. The eigenvalues, $\epsilon_{nl}(\delta)$, are given in the form of Taylor series in $\delta$ which can be systematically calculated to the desired order $\delta^{k}$. Coulomb $l$-degeneracy is broken by the screening effects and, for a given $n$, $\epsilon_{nl}(\delta)$ is larger for higher values of $l$, which causes the crossing of levels for $n\ge4$. The convergence radius of the Taylor series can be enlarged up to the critical values using the Padé approximants technique, which allows us to calculate the eigenvalues with high precision in the whole range of values of $\delta$ where bound states exist, and to reach a precise determination of the critical screening lengths, $\delta_{nl}$. Eigenstates have a form similar to the solutions of the Coulomb potential, with the associated Laguerre polynomials replaced by new polynomials of order $\delta^{k}$ with $r$-dependent coefficients which, in turn, are polynomials in $r$. In general we find sizable deviations from the Coulomb radial probabilities only for screening lengths close to their critical values. We use these solutions to find the squared absolute value at the origin of the wave function for $l=0$, and their derivatives for $l=1$, for the lowest states, as functions of $\delta$, which enter the phenomenology of dark matter bound states in dark gauge theories with a light dark mediator.