bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity and liver disease affect the fat-free mass in adolescents with cystic fibrosis
Authors: Dassios Theodore , Mitakidou Maria Rafaela , Dhawan Anil , Papalexopoulou Niovi , Gupta Atul , Greenough Anne
Published: December 2022

Cystic fibrosis (CF) is predominantly a lung disease but is also characterised by impaired skeletal muscularity and a reduction in fat-free mass. We aimed to test the hypothesis that clinical and anthropometric parameters would determine fat-free mass impairment in adolescents with CF. We measured the fat-free mass index (FFMI) using bioelectrical impedance, the lung function using spirometry, the number of shuttles as a measure of exercise tolerance and the reported physical activity in children and young people with CF in a tertiary centre at King’s College Hospital, London, UK. CF-related liver disease was diagnosed by abnormal liver enzymes and/or ultrasonography. We studied 28 children and young people (11 male) with a median (interquartile range (IQR)) age of 15 (13–17) years. They had a median (IQR) FFMI of 13.5 (11.6–15.1) kg/m2. The FFMI significantly correlated with age (rho = 0.568,p = 0.002), number of shuttles (rho = 0.691,p < 0.001) and reported hours of activity per day (rho = 0.426,p = 0.024). The median (IQR) FFMI was significantly higher in male [15.1 (13.1–18.6) kg/m2] compared to female participants [12.7 (11.6–14.1) kg/m2,p = 0.008]. The median (IQR) FFMI was significantly lower in the 10 (36%) participants with liver disease [11.9 (11.5–13.4) kg/m2] compared to the FFMI in the remaining 18 participants without liver disease [14.4 (12.5–15.9) kg/m2,p = 0.027].

Conclusion: Fat-free mass increases with increasing age and growth in adolescents with CF. Physical activity exerts a beneficial effect on fat-free mass, and CF-related liver disease negatively affects fat-free mass in adolescents with CF.What is Known:• Health behaviours in adolescence influence lifelong health in cystic fibrosis (CF).• A normal body mass index in CF might fail to reveal a low fat-free mass (FFM), and quality of life in CF is strongly associated with a reduced FFM.What is New:• FFM increases with increasing age and growth in adolescents with CF.• Physical activity exerts a beneficial effect, and liver disease negatively affects FFM in adolescents with CF.
Targeting de novo loss-of-function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project
Authors: Seaby Eleanor G. , Thomas N. Simon , Webb Amy , Brittain Helen , Taylor Tavares Ana Lisa ,   Genomics England Consortium, Ambrose J. C. , Arumugam P , Bevers R , Bleda M , Boardman-Pretty F , Boustred C. R. , Brittain H , Caulfield M. J. , Chan G. C. , Fowler T , Giess A , Hamblin A , Henderson S , Hubbard T. J. P. , Jackson R , Jones L. J. , Kasperaviciute D , Kayikci M , Kousathanas A , Lahnstein L. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F , McEntagart M. , Minneci F , Moutsianas L , Mueller M. , Murugaesu N , Need A. C. , O‘Donovan P. , Odhams C. A. , Patch C , Perez-Gil D , Pereira M. B. , Pullinger J , Rahim T , Rendon A , Rogers T , Savage K , Sawant K , Scott R. H. , Siddiq A , Sieghart A , Smith S. C. , Sosinsky A , Stuckey A , Tanguy M , Taylor Tavares A. L. , Thomas E. R. A. , Thompson S. R. , Tucci A , Welland M. J. , Williams E , Witkowska K , Wood S. M. , Baralle Diana , Rehm Heidi L. , O’Donnell-Luria Anne , Ennis Sarah
Published: December 2022

Background

Genome sequencing was first offered clinically in the UK through the 100,000 Genomes Project (100KGP). Analysis was restricted to predefined gene panels associated with the patient’s phenotype. However, panels rely on clearly characterised phenotypes and risk missing diagnoses outside of the panel(s) applied. We propose a complementary method to rapidly identify pathogenic variants, including those missed by 100KGP methods.

Methods

The Loss-of-function Observed/Expected Upper-bound Fraction (LOEUF) score quantifies gene constraint, with low scores correlated with haploinsufficiency. We applied DeNovoLOEUF, a filtering strategy to sequencing data from 13,949 rare disease trios in the 100KGP, by filtering for rare, de novo, loss-of-function variants in disease genes with a LOEUF score < 0.2. We compared our findings with the corresponding patient’s diagnostic reports.

Results

324/332 (98%) of the variants identified using DeNovoLOEUF were diagnostic or partially diagnostic (whereby the variant was responsible for some of the phenotype). We identified 39 diagnoses that were “missed” by 100KGP standard analyses, which are now being returned to patients.

Conclusion

We have demonstrated a highly specific and rapid method with a 98% positive predictive value that has good concordance with standard analysis, low false-positive rate, and can identify additional diagnoses. Globally, as more patients are being offered genome sequencing, we anticipate that DeNovoLOEUF will rapidly identify new diagnoses and facilitate iterative analyses when new disease genes are discovered.
External validation of risk prediction scores in patients undergoing anatomic video-assisted thoracoscopic resection
Authors: Ponholzer Florian , Chorazy Karol , Ng Caecilia , Kocher Florian , Maier Herbert , Lucciarini Paolo , Öfner Dietmar , Augustin Florian
Published: December 2022

Background

EuroLung Risk scores were established to predict postoperative morbidity and mortality in patients undergoing anatomic lung resections. We aimed to perform an external validation of the EuroLung scores, which were calculated from data of the European Society of Thoracic Surgeons database, in our video-assisted thoracoscopic surgery cohort.

Methods

All available EuroLung scores were calculated for 718 patients scheduled for anatomic video-assisted thoracoscopic surgery resections between 2009 and 2019. Morbidity and mortality according to the definitions of the EuroLung scores were analyzed in a prospectively maintained database.

Results

Overall observed complication rate was 10.45%. Scores showed weak individual correlation (η = 0.155–0.174). The EuroLung1 app score showed the biggest area under the receiver operative characteristic (ROC) curve with 0.660. Binary logistic regression analysis showed that predicted postoperative forced expiratory volume in 1 s was associated with increased complications in both EuroLung1 and parsimonious EuroLung1 scores. Thirty-day mortality was 0.7% (predicted 1.10–1.40%) and was associated with predicted postoperative forced expiratory volume in 1 s for both EuroLung2 and parsimonious EuroLung2 scores. The EuroLung2 (2016) showed the biggest area under the ROC curve with 0.673. Only a very weak eta correlation between predicted and observed mortality was found for both aggregate EuroLung2, EuroLung2 (2016), EuroLung2 (2019), and parsimonious EuroLung2 (2016) (η = 0.025/0.015/0.011/0.009).

Conclusion

EuroLung scores help to estimate postoperative morbidity. However, even with the highest aggregate EuroLung scores possible only 50% suffer from postoperative morbidity. Although calibration of the scores was acceptable, discrimination between predicted and observed events was poor. Therefore, individual correlation between predicted and observed events is weak. Therefore, EuroLung scores may be best used to compare institutional quality of care to the European Society of Thoracic Surgeons database but should not be used to preclude patients from surgical treatment.
External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort
Authors: Antkowiak Lukasz , Rogalska Marta , Stogowski Piotr , Bruzzaniti Placido , Familiari Pietro , Rybaczek Magdalena , Klepinowski Tomasz , Grzyb Weronika , Zimny Mikolaj , Weclewicz Mateusz , Kasperczuk Anna , Kloc Wojciech , Rudnik Adam , Sagan Leszek , Lyson Tomasz , Mariak Zenon , Santoro Antonio , Mandera Marek
Published: December 2022

Purpose

While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales.

Methods

A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year.

Results

Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively.

Conclusion

The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.
A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel
Authors: Saeed Kordo , Ahmad-Saeed Nusreen , Annett Rachel , Barlow Gavin , Barrett Lucinda , Boyd Sara E. , Boran Nicola , Davies Peter , Hughes Harriet , Jones Gwennan , Leach Laura , Lynch Maureen , Nayar Deepa , Maloney Robert J. , Marsh Martin , Milburn Olivia , Mitchell Shanine , Moffat Lynn , Moore Luke S. P. , Murphy Michael E. , O’Shea Shaan Ashk , O’Sullivan Fionnuala , Peach Teresa , Petridou Christina , Reidy Niamh , Selvaratnam Mathyruban , Talbot Ben , Taylor Vanessa , Wearmouth Deborah , Aldridge Catherine
Published: December 2022

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.
Mathematics of 2-Dimensional Lattices
Authors: Kurlin Vitaliy
Published: December 2022

A periodic lattice in Euclidean space is the infinite set of all integer linear combinations of basis vectors. Any lattice can be generated by infinitely many different bases. This ambiguity was partially resolved, but standard reductions remain discontinuous under perturbations modelling atomic displacements. This paper completes a continuous classification of 2-dimensional lattices up to Euclidean isometry (or congruence), rigid motion (without reflections), and similarity (with uniform scaling). The new homogeneous invariants allow easily computable metrics on lattices considered up to the equivalences above. The metrics up to rigid motion are especially non-trivial and settle all remaining questions on (dis)continuity of lattice bases. These metrics lead to real-valued chiral distances that continuously measure lattice deviations from higher-symmetry neighbours. The geometric methods extend the past work of Delone, Conway, and Sloane.
Seismic fatality risk evaluation framework for existing buildings in Switzerland
Authors: Arslantürkoglu Safak , Stojadinovic Bozidar
Published: December 2022

The Swiss code SIA 269/8 for the seismic evaluation of existing structures is risk-based. It relies on the compliance factor αeff, defined as the ratio of the seismic capacity of an existing structure to the required seismic capacity of a hypothetical identical new structure, to indirectly evaluate the casualty risk posed by the existing structure. While it is convenient to have a direct relationship between the casualty risk and the degree of code compliance of the existing structure, it is debatable if the contributions of the seismic hazard, structural performance and occupancy to the casualty risk should be merged into a single quantity, conflicting with the multi-component nature of seismic risk. This paper presents a graphical framework to evaluate the seismic fatality risk for existing buildings. The framework is based on the PEER Center performance-based earthquake engineering methodology to provide a transparent view of the contributions of different sources of hazard and risk. Starting from a seismic hazard model, probabilistic seismic demand, damage and loss models are introduced, taking the uncertainty into account at each step. The final product of the proposed framework, a loss curve representing the (annual) exceedance rate of fatality counts, enables engineers and building owners to make better, risk-based decisions. The proposed framework is demonstrated for an existing building in Switzerland. Notably, in addition to the SIA 269/8 evaluation method, this demonstration compares eight hybrid approaches differentiated by the utilized structural assessment techniques (nonlinear static pushover vs. incremental dynamic analysis), uncertainty propagation in the demand model (record variability only vs. record variability and epistemic uncertainty) and solution strategies (closed-form vs. numerical) to find a practical compromise between the accuracy and the computational effort. A comparison of the obtained results shows that the SIA 269/8 evaluation method underestimates the fatality risk for the presented building and identifies a practical alternative based on the proposed graphical framework.
Reflections on Turkish Personal Data Protection Law and Genetic Data in Focus Group Discussions
Authors: Özkan Özlem , Şahinol Melike , Aydinoglu Arsev Umur , Aydin Son Yesim
Published: December 2022

Since the 1970s and more rigorously since the 1990s, many countries have regulated data protection and privacy laws in order to ensure the safety and privacy of personal data. First, a comparison is made of different acts regarding genetic information that are in force in the EU, the USA, and China. In Turkey, changes were adopted only recently following intense debates. This study aims to explore the experts’ opinions on the regulations of the health information systems, data security, privacy, and confidentiality in Turkey, with a particular focus on genetic data, which is more sensitive than other health data as it is a permanent identifier that is inherited to next of kin and shared with other family members. Two focus groups with 18 experts and stakeholders were conducted, discussing topics such as central data collection, legalized data sharing, and the management of genetic information in health information systems. The article concludes that the new Turkish personal data protection law is problematic as the frame of collectible data is wide-ranging, and the exceptions are extensive. Specific laws or articles dedicated to genetic data that also overlook the dimension of discrimination based on genetic differences in Turkey should be taken into consideration. In broader terms, it is intended to put up for discussion that in addition to ethical aspects, economic aspects and legal aspects of health should be included in the discussion to be carried out within the framework of socio-political analyses with culture-specific approaches and cross-culture boundaries simultaneously.
Establishment and characterization of urothelial carcinoma cell lines with and without BRAF mutation (V595E) in dogs
Authors: Yamasaki Hirofumi , Uematsu Yosuke , Okano Kumiko , Ichikawa Mika , Tei Meina , Hirabayashi Miyuki , Uchida Kazuyuki , Ono Kenichiro , Hirao Hidehiro
Published: December 2022

Each 5 urothelial carcinoma (UC) cell lines with and without the v-Raf murine sarcoma virus oncogene homolog B (BRAF) gene mutation (V595E) were established and examined V595E-related tumorigenic characteristics in dogs. No typical morphological features were observed in cloned cells with and without V595E. The cell proliferation of both cloned cells showed logarithmic growth curve and those doubling time were 24.9 ± 4.1 h in V595E ( +) and 29.3 ± 11.3 h in V595E ( −). On the growth curve of xenotransplanted tumor in severe combined immunodeficiency mice, 3 out of 5 V595E ( +) and 2 out of 5 V595E ( −) cloned cells revealed gradually and remarkably increasing curve, indicating clearly tumorigenicity. The xenotransplanted tumors with V595E ( +) showed typical features of UC, such as solid proliferation of pleomorphic tumor cells, formation of papillary structure, and glandular structure. Additionally, various vascular formation was observed, probably indicating an advanced growth phase of UC. In mitogen-activated protein kinase (MAPK) signaling pathway, cytoplasmic phosphorylated-BRAF (pBRAF) and cytoplasmic and nuclear phosphorylated-ERK1/2 (pERK1/2) were detected in all 4 tumors with V595E ( +), whereas only cytoplasmic and nuclear pERK1/2 was detected in tumors with V595E ( −). Since V595E can directly activate MAPK signaling pathway, coincidence of V595E with pBRAF (phosphor Thr598/Ser601) indicates acquired resistance to BRAF inhibitors. These established UC cell lines, especially V595E ( +) cell lines, are useful tool for understanding pathophysiological states and controlling therapeutic manners of UC in dogs.
What is mathematics teaching talk for? A response based on three sites of practice in mathematics education
Authors: Planas Núria , Adler Jill , Mwadzaangati Lisnet
Published: December 2022

During the last decades, the study of how learners and teachers of mathematics use the resource of language has contributed to our understanding of mathematics teaching and learning in a variety of classrooms and cultures. Developmental work with mathematics teachers on the particular resource of mathematics teaching talk is more recent. In order to explore responses related to the importance of this talk, in this paper we consider three sites of practice in mathematics education—research, professional development and teaching—and illustrations of data from or about them, including studies from the literature, and work with secondary school mathematics teachers in Catalonia-Spain and Malawi around the teaching of angles. We argue that tensions permeate these sites of practice when a focus is placed on word use, specifically the practices of naming and explaining, in mathematics teaching talk. We conclude that the importance of mathematics teaching talk is construed through tensions with other resources in language and teaching. Tensions specifically appear in the realisation of mathematics teaching talk as mediational in the work with mathematics teachers on their classroom teaching.
Responsible Innovation and De Jure Standardisation: An In-Depth Exploration of Moral Motives, Barriers, and Facilitators
Authors: Wiarda Martijn , van de Kaa Geerten , Doorn Neelke , Yaghmaei Emad
Published: December 2022

Standardisation is increasingly seen as a means to insert ethics in innovation processes. We examine the institutionalisation of responsible innovation in de jure standardisation as this is an important but unexplored research area. In de jure standardisation, stakeholders collaborate in committees to develop standards. We adopt the anticipation, inclusion, reflexivity, and responsiveness responsible innovation framework as our theoretical lens. Our study suggests that responsible standardisation processes should embody forms of these four dimensions. We investigate the institutionalisation of these dimensions and identify 96 factors that can motivate, hinder, or facilitate responsible standardisation. Factors were found through in-depth interviews with managers of a standard developing organisation. These are subsequently validated/rejected using surveys completed by committee representatives. The results suggest that the social desirability of standards is not self-evident. This study could pave the way for future research on responsible standardisation processes, complementing research on legitimacy, responsible innovation, and standardisation.
Medical students’ career decision-making stress during clinical clerkships
Authors: Fris Daan A. H. , Van Vianen Annelies E. M. , Koen Jessie , De Hoog Matthijs , De Pagter Anne P. J.
Published: December 2022

Objectives Many medical students experience career decision-making stress in the
final phase of training. Yet, the factors that induce or reduce career decision- making
stress and how progression in their clerkships relates to these factors are unknown.
This knowledge gap limits the possibilities for medical schools to develop and implement
interventions targeting students’ career decision-making stress. This study explores
content, process, and context factors that may affect career decision-making
stress.
Methods Using cross-sectional survey data from medical master students (n=
507), we assessed content (future work self ), process (choice irreversibility, time
pressure, career decision-making self-efficacy), and context (supervisory support,
medical school support, study load, competition) factors and their relationships with
career decision-making stress. The hypothesized relationships were tested with
structural equation modelling.
 Results A clearer future work self and higher
career decision self-efficacy were associated with lower career decision-making stress,
while experienced time pressure, competition, and study load were associated with higher
career decision-making stress. Choice-irreversibility beliefs, supervisory support, and
medical school support were unrelated to career decision-making stress. As students’
clerkships progressed, they gained a clearer future work self, but also experienced more
time pressure.
Discussion Clinical clerkships help students to form a clearer
future work self, which can diminish career decision-making stress. Yet, students also
experience more time pressure as the period of clerkships lengthens, which can increase
career decision-making stress. A school climate of high competition and study load seems
to foster career decision-making stress, while school support hardly seems effective in
diminishing this stress.
Harnessing a knowledge translation framework to implement an undergraduate medical
education intervention: A longitudinal study
Authors: Chamberland Martine , Setrakian Jean , Bergeron Linda , Varpio Lara , St-Onge Christina , Thomas Aliki
Published: December 2022

Introduction Implementation of evidence-informed educational interventions (EEI)
involves applying and adapting theoretical and scientific knowledge to a specific
context. Knowledge translation (KT) approaches can both facilitate and structure the
process. The purpose of this paper is to describe lessons learned from applying a KT
approach to help implement an EEI for clinical reasoning in medical students.

Methods Using the Knowledge to Action framework, we designed and implemented an EEI
intended to support the development of students’ clinical reasoning skills in a renewed
medical curriculum. Using mixed-methods design, we monitored students’ engagement with
the EEI longitudinally through a platform log; we conducted focus groups with students
and stakeholders, and observed the unfolding of the implementation and its continuation.
Data are reported according to six implementation outcomes: Fidelity, Feasibility,
Appropriateness, Acceptability, Adoption, and Penetration.
Results Students spent a
mean of 24min on the activity (fidelity outcome) with a high completion rate (between
75% and 95%; feasibility outcome) of the entire activity each time it was done. Focus
group data from students and stakeholders suggest that the activity was acceptable,
appropriate, feasible, adopted and well-integrated into the curriculum.
Occurrence of Iron in the Minerals of Carboniferous Coal Gangue of the Pingshuo Open-pit Mine, North China
Authors: Liu Lihui , Liu Qinfu , Li Yakui , Cao Haiyue , Kang Xingjian
Published: December 2022

The state of iron in coal gangue minerals is an important factor in determining the potential for value-added utilization of this solid waste; this is especially true for the coal gangue coming from the Pingshuo open-pit mine in China. The objective of the present study was to characterize the petrological, mineralogical, and chemical states of Fe in the coal gangue from the Carboniferous Taiyuan Formation. Methods used included polarizing microscopy, X-ray diffraction (XRD), scanning electron microscopy–energy-dispersive spectroscopy (SEM–EDS), X-ray fluorescence, micro-Fourier-transform infrared (micro-FTIR) spectroscopy, and Mössbauer spectroscopy. The coal gangues are mudstones, silty mudstones, and pelitic siltstones, which are composed primarily of kaolinite, quartz, feldspar, pyrite, illite, and magnesite. In coal gangue, the Fe was found to occur in ferruginous minerals, in crystal-lattice substitutions, or in a colloidal state. The ferruginous minerals in the coal gangue are pyrite and marcasite, and the pyrite morphologies are framboidal, euhedral octahedral crystals, subhedral granular crystals, and irregular crystals. The results of SEM–EDS and micro-FTIR confirmed that the lattice substitution of Fe in the coal gangue minerals occurred mainly in kaolinite, resulting in two types of kaolinite: iron-containing and iron-free kaolinite. The former may be transformed from volcanic biotite and the latter from volcanic feldspar. The Mössbauer spectra of kaolinite showed intense doublets with isomer shift and quadrupole splitting values consistent with tetrahedrally coordinated Fe3+ and ocahedrally coordinated Fe2+, suggesting the presence of two types of substitution sites: (1) Fe2+ replacing Al3+ in the octahedral sheet; and (2) Fe3+ replacing Si4+ in the tetrahedral sheet. This study has important theoretical significance for the high-value utilization of coal gangue.
The impact of consanguinity on human health and disease with an emphasis on rare diseases
Authors: Temaj G. , Nuhii N. , Sayer J. A.
Published: December 2022

Purpose

Consanguinity increases the likelihood of the inheritance of homozygous pathogenic alleles which may predispose to rare autosomal recessive disorders. Here we discuss the role of consanguinity in informing inherited disease with a focus on rare diseases.

Methods

We reviewed the literature concerning the impact of consanguinity on human diseases and chose examples to illustrate the most important themes.

Results

Consanguinity rates vary hugely between different populations influencing the prevalence of rare autosomal recessive diseases. Some founder genetic variants leading to human disease are specific for a single country, or a specific ethnic or geographic group while others are shared more widely. Inherited diseases of known molecular genetic etiology are characterized by their genotype and phenotype but many exhibit marked heterogeneity which may be population dependent. Increased rates of consanguinity are associated with rare autosomal recessive inherited diseases and can lead to more than one human genetic disease in affected individuals leading to complex and overlapping phenotypes. Next-generation sequencing strategies allow new insights into these cases. In contrast, the impact of consanguinity on malignancies and common multifactorial diseases is less predictable and needs further exploration.

Conclusions

High rates of consanguinity remain prevalent in certain populations and lead to an increased burden of rare autosomal recessive inherited diseases. Strategies to reduce consanguinity are needed to reduce these disease consequences and will require global improvements in education, social, and economic conditions.
UMOD and you! Explaining a rare disease diagnosis
Authors: Mabillard Holly , Olinger Eric , Sayer John A.
Published: December 2022

The precise molecular genetic diagnosis of a rare inherited disease is nearly always a prolonged odyssey. Fortunately, modern molecular testing strategies are allowing more diagnoses to be made. There are many different rare inherited kidney diseases and both the genetic heterogeneity of these conditions and the clinical diversity often leads to confusing nomenclature. Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an example of this. ADTKD, an inherited kidney disease that leads to worsening of kidney function over time, often culminating in end stage kidney disease, accounting for around 2% of this cohort. UMOD is the most common gene implicated in this disorder but there are at least 6 subtypes. At present, there are no specific treatments for ADTKD. Here, we review the current understanding of this condition and provide patient-centred information to allow conceptual understanding of this disease to allow better recognition, diagnosis and management.
Using a multicultural and multilingual awareness-raising strategy to enhance enrollment of racially underrepresented minoritized communities – the PassITON trial
Authors: Bell Jasmine , Cook Sarah , Edwards Terri L. , Rice Todd W. , Self Wesley H. , Wheeler Allison , Rhoads Jillian , Stewart Thomas G. , Pulley Jill M. , Benhoff Katelyn , Harris Paul A. , Wilkins Consuelo
Published: December 2022

Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.
Direct numerical simulation of turbulent open channel flows at moderately high Reynolds numbers
Authors: Yao Jie , Chen Xi , Hussain Fazle
Published: December 2022

Well-resolved direct numerical simulations of turbulent open channel flows (OCFs) are performed for friction Reynolds numbers up to

$Re_\tau =2000$

. Various turbulent statistics are documented and compared with the closed channel flows (CCFs). As expected, the mean velocity profiles of the OCFs match well with the CCFs in the near-wall region but diverge notably in the outer region. Interestingly, a logarithmic layer with Kárman constant

$\kappa =0.363$

occurs for OCF at

$Re_\tau =2000$

, distinctly different from CCF. Except for a very thin layer near the free surface, most of the velocity and vorticity variances match between OCFs and CCFs. The one-dimensional energy spectra reveal that the very-large-scale motions (VLSMs) with streamwise wavelength

$\lambda _x>3 h$

or spanwise wavelength

$\lambda _z>0.5 h$

contribute the most to turbulence intensity and Reynolds shear stress in the overlap and outer layers (where h is the water depth). Furthermore, the VLSMs in OCFs are stronger than those in CCFs, resulting in a slightly higher streamwise velocity variance in the former. Due to the footprint effect, these structures also have significant contributions to the mean wall shear stress, and the difference between OCF and CCF enlarges with increasing

$Re_\tau$

. In summary, the free surface in OCFs plays an essential role in various flow phenomena, including the formation of stronger VLSMs and turbulent kinetic energy redistribution.
Sixty years of ice form and flow at Camp Century, Greenland
Authors: Colgan William , Jakobsen Jakob , Solgaard Anne , Løkkegaard Anja , Abermann Jakob , Khan Shfaqat A. , Csatho Beata , MacGregor Joseph A. , Fausto Robert S. , Karlsson Nanna , Pedersen Allan Ø. , Andersen Signe B. , Sonntag John , Hvidberg Christine S. , Ahlstrøm Andreas P.
Published: December 2022

The magnitude and azimuth of horizontal ice flow at Camp Century, Greenland have been measured several times since 1963. Here, we provide a further two independent measurements over the 2017–21 period. Our consensus estimate of horizontal ice flow from four independent satellite-positioning solutions is 3.65 ± 0.13 m a−1at an azimuth of 236 ± 2°. A portion of the small, but significant, differences in ice velocity and azimuth reported between studies likely results from spatial gradients in ice flow. This highlights the importance of restricting inter-study comparisons of ice flow estimates to measurements surveyed within a horizontal distance of one ice thickness from each other. We suggest that ice flow at Camp Century is stable on seasonal to multi-decadal timescales. The airborne and satellite laser altimetry record indicates an ice thickening trend of 1.1 ± 0.3 cm a−1since 1994. This thickening trend is qualitatively consistent with previously inferred ongoing millennial-scale ice thickening at Camp Century. The ice flow divide immediately north of Camp Century may now be migrating southward, although the reasons for this divide migration are poorly understood. The Camp Century flowlines presently terminate in the vicinity of Innaqqissorsuup Oqquani Sermeq (Gade Gletsjer) on the Melville Bay coast.
On intersection probabilities of four lines inside a planar convex domain
Authors: Martirosyan Davit , Ohanyan Victor
Published: December 2022

Let
$n\geq 2$
random lines intersect a planar convex domain D. Consider the probabilities
$p_{nk}$
,
$k=0,1, \ldots, {n(n-1)}/{2}$
that the lines produce exactly k intersection points inside D. The objective is finding
$p_{nk}$
through geometric invariants of D. Using Ambartzumian’s combinatorial algorithm, the known results are instantly reestablished for
$n=2, 3$
. When
$n=4$
, these probabilities are expressed by new invariants of D. When D is a disc of radius r, the simplest forms of all invariants are found. The exact values of
$p_{3k}$
and
$p_{4k}$
are established.
The President Will See Whom Now? Presidential Engagement with Organized Interests
Authors: MILLER DAVID RYAN
Published: December 2022

Though presidents often criticize organized interests, presidents also expend considerable effort engaging them. Using original elite interviews, a survey of lobbyists, and administrative data, I consider how this engagement manifests, why presidents engage interests, and with which interests presidents engage. Unlike in other institutions, presidents exercise substantial control over engagement with interests, and they engage to mobilize interests’ institutional resources in service of their goals. To optimize mobilization, presidents focus engagement on well-resourced interests and interests who share presidents’ preferences. Pairing over seven million White House visitor log entries from two administrations with lobbying and campaign finance records, I demonstrate that presidential engagement is informed by interests’ electoral and policy resources and partisan alignment, though these characteristics’ substantive effects are modest. My findings highlight coalition building with interests as an underappreciated source of presidential power and elucidate the degree to which presidents amplify the political voice of well-resourced and copartisan interests.
Contracting Welfare Services to Social Organizations in China: Multiple Logics
Authors: Qu Yuanyuan , Howell Jude , Enjuto Martinez Regina
Published: December 2022

As part of a broader direction of welfare and governance reforms, China has launched a policy to contract welfare services out to social organizations. Scholars have explored the implementation of the policy in a few socioeconomically advanced cities such as Guangzhou, Shenzhen and Shanghai. In this article, we examine how local governments lacking nongovernmental services suppliers or resources for contracting respond to the policy. We developed a framework of multiple logics to analyse services contracting in a county-level city in eastern China. We found that local officials follow three logics in implementing the policy: to meet the central state's targets, to balance policy outcomes and risks, and to stimulate a more participatory society. This generates a mix of policy behaviour, including entrepreneurialism, welfarism, innovation, risk-sharing and collaboration. We thus argue the interplay of the logics determines the local policy process of services contracting in China.
The Roman Republican castellum of Puig Castellar (Biosca): the earliest evidence for military headquarters in Hispania Citerior (180–120 BCE)
Authors: Rodrigo Esther , Romaní Núria , Carreras Cesar , Pera Joaquim , Catarineu Laia
Published: December 2022

This paper illustrates the results of research carried out at the archaeological site of Puig Castellar de Biosca (Catalonia, Spain), located in the northeast of the Iberian Peninsula. This Republican military fortress, a castellum, is exceptional due both to its early chronology, which ranges between 180 and 120 BCE, and to the fact that it acted as a long-lasting military installation situated in a pacified area on the periphery of the Celtiberian conflict zone. Work at the site has uncovered a central building on the top of a hill, which due to its Italian features has been identified as the headquarters of the military fortress. If this interpretation is correct, this might be one of the first examples of a Republican military headquarters building documented to date. It could then be considered a predecessor of later praetoria and principia, which have been recorded in the Numantine camps and on the Roman westernlimes.
Taking a Closer Look at the Bayesian Truth Serum
Authors: Schoenegger Philipp , Verheyen Steven
Published: December 2022

Abstract. Over the past few decades, psychology and its cognate disciplines have undergone substantial scientific reform, ranging from advances in statistical methodology to significant changes in academic norms. One aspect of experimental design that has received comparatively little attention is incentivization, i.e., the way that participants are rewarded and incentivized monetarily for their participation in experiments and surveys. While incentive-compatible designs are the norm in disciplines like economics, the majority of studies in psychology and experimental philosophy are constructed such that individuals’ incentives to maximize their payoffs in many cases stand opposed to their incentives to state their true preferences honestly. This is in part because the subject matter is often self-report data about subjective topics, and the sample is drawn from online platforms like Prolific or MTurk where many participants are out to make a quick buck. One mechanism that allows for the introduction of an incentive-compatible design in such circumstances is the Bayesian Truth Serum (BTS; Prelec, 2004 ), which rewards participants based on how surprisingly common their answers are. Recently, Schoenegger (2021) applied this mechanism in the context of Likert-scale self-reports, finding that the introduction of this mechanism significantly altered response behavior. In this registered report, we further investigate this mechanism by (1) attempting to directly replicate the previous result and (2) analyzing if the Bayesian Truth Serum’s effect is distinct from the effects of its constituent parts (increase in expected earnings and addition of prediction tasks). We fail to find significant differences in response behavior between participants who were simply paid for completing the study and participants who were incentivized with the BTS. Per our pre-registration, we regard this as evidence in favor of a null effect of up to V = .1 and a failure to replicate but reserve judgment as to whether the BTS mechanism should be adopted in social science fields that rely heavily on Likert-scale items reporting subjective data, seeing that smaller effect sizes might still be of practical interest and results may differ for items different from the ones we studied. Further, we provide weak evidence that the prediction task itself influences response distributions and that this task’s effect is distinct from an increase in expected earnings, suggesting a complex interaction between the BTS’ constituent parts and its truth-telling instructions.
Space–Time Congruency Effects Using Eye Movements During Processing of Past- and Future-Related Words
Authors: Grasso Camille L. , Ziegler Johannes C. , Coull Jennifer T. , Montant Marie
Published: December 2022

Abstract. In Western cultures where people read and write from left to right, time is represented along a spatial continuum that goes from left to right (past to future), known as the mental timeline (MTL). In language, this MTL was supported by space–time congruency effects: People are faster to make lexical decisions to words conveying past or future information when left/right manual responses are compatible with the MTL. Alternatively, in cultures where people read from right to left, space–time congruency effects go in the opposite direction. Such cross-cultural differences suggest that repeated writing and reading dynamic movements are critically involved in the spatial representation of time. In most experiments on the space–time congruency effect, participants use their hand for responding, an effector that is associated to the directionality of writing. To investigate the role of the directionality of reading in the space–time congruency effect, we asked participants to make lateralized eye movements (left or right saccades) to indicate whether stimuli were real words or not (lexical decision). Eye movement responses were slower and higher in amplitude for responses incompatible with the direction of the MTL. These results reinforce the claim that repeated directional reading and writing movements promote the embodiment of time-related words.
Sea Level and Socioeconomic Uncertainty Drives High‐End Coastal Adaptation Costs
Authors: Wong T. E. , Ledna C. , Rennels L. , Sheets H. , Errickson F. C. , Diaz D. , Anthoff D.
Published: December 2022

Sea‐level rise and associated flood hazards pose severe risks to the millions of people globally living in coastal zones. Models representing coastal adaptation and impacts are important tools to inform the design of strategies to manage these risks. Representing the often deep uncertainties influencing these risks poses nontrivial challenges. A common uncertainty characterization approach is to use a few benchmark cases to represent the range and relative probabilities of the set of possible outcomes. This has been done in coastal adaptation studies, for example, by using low, moderate, and high percentiles of an input of interest, like sea‐level changes. A key consideration is how this simplified characterization of uncertainty influences the distributions of estimated coastal impacts. Here, we show that using only a few benchmark percentiles to represent uncertainty in future sea‐level change can lead to overconfident projections and underestimate high‐end risks as compared to using full ensembles for sea‐level change and socioeconomic parametric uncertainties. When uncertainty in future sea level is characterized by low, moderate, and high percentiles of global mean sea‐level rise, estimates of high‐end (95th percentile) damages are underestimated by between 18% (SSP1‐2.6) and 46% (SSP5‐8.5). Additionally, using the 5th and 95th percentiles of sea‐level scenarios underestimates the 5%–95% width of the distribution of adaptation costs by a factor ranging from about two to four, depending on SSP‐RCP pathway. The resulting underestimation of the uncertainty range in adaptation costs can bias adaptation and mitigation decision‐making.
Investigation of the ΣO/N2 Depletion With Latitudinally Tilted Equatorward Boundary Observed by GOLD During the Geomagnetic Storm on April 20, 2020
Authors: Yu Tingting , Cai Xuguang , Ren Zhipeng , Li Shaoyang , Pedatella Nicholas , He Maosheng
Published: December 2022

A long‐lived (>10 hr) O/N2 column density ratio (∑O/N2) depletion at middle latitudes was observed by the Global‐scale Observations of the Limb and Disk (GOLD) during the 20 April 2020 geomagnetic storm. The observed ∑O/N2 depletion tilts latitudinally at equatorward boundary with the lowest latitude of ∼20°N at ∼75°W, and changes orientation near 75°W, with a north‐westward tilt to the west of ∼75W and a north‐eastward tilt to the east of ∼75W. The National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model shows the similar ∑O/N2 depletion patterns and magnitudes, but the longitudes with the most equatorward were ∼100°W and moved westward from ∼100°W to ∼140°W during the storm recovery period. Horizontal winds play major role in forming this middle‐latitude ∑O/N2 depletion structure. The strongest equatorward winds in the longitude sector near the magnetic pole resulted in the most equatorward expansion of all longitudes, generating the depletion with latitudinally tilted equatorward boundary. In addition, the high‐latitude westward zonal wind and the middle‐latitude eastward zonal wind maintained the long existence of this depletion in the GOLD Field of View. The further analysis on neutral winds shows that storm‐time meridional winds at middle latitudes in the mid‐low thermosphere are mainly dominated by pressure gradient force, while zonal winds are determined primarily by horizontal momentum advection.
Composition of Mars's Dayside Ionosphere Under Changing Solar Irradiance Conditions
Authors: Hensley K. , Withers P. , Thiemann E.
Published: December 2022

The response of the Mars ionosphere to changes in solar irradiance is an important aspect of how conditions on Mars are shaped by our dynamic Sun. Changes in the composition of ionospheric plasma with changes in solar irradiance will affect how the ionosphere mediates the interaction of the neutral atmosphere with the surrounding space environment. Here we use MAVEN ion and neutral density measurements acquired at low (Deep Dip 8) and high (Deep Dip 2) solar irradiance conditions to determine how ion and neutral densities change when the ionizing solar irradiance doubles. We find that the neutral composition does not change significantly when examined at fixed total neutral number density. Furthermore, we find that and O+ densities increase by a factor of 2, but densities increase by a factor of 1.5. The relative abundance of decreases as solar irradiance increases. These results are explained by straightforward theoretical considerations of changes in ion production and loss rates. However, a photochemical model fails to reproduce these results with its default set of inputs. Consistent with previous modeling efforts, densities are over‐predicted. Acceptable model–data agreement requires significant adjustments to important model inputs, such as reduction in irradiance by 15%, reduction in CO2 density by a factor of 2, and increase in O density by a factor of 2. These large adjustments are suggestive of the need for improvements to the state of Mars ionosphere models based on MAVEN inputs rather than issues with the underlying data.