bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse AD at Higher Types: Pure, Principled and Denotationally Correct
Authors: Vákár Matthijs
Published: March 2021

We show how to define forward- and reverse-mode automatic differentiation source-code transformations or on a standard higher-order functional language. The transformations generate purely functional code, and they are principled in the sense that their definition arises from a categorical universal property. We give a semantic proof of correctness of the transformations. In their most elegant formulation, the transformations generate code with linear types. However, we demonstrate how the transformations can be implemented in a standard functional language without sacrificing correctness. To do so, we make use of abstract data types to represent the required linear types, e.g. through the use of a basic module system.
Coupled Relational Symbolic Execution for Differential Privacy
Authors: Farina Gian Pietro , Chong Stephen , Gaboardi Marco
Published: March 2021

Differential privacy is a de facto standard in data privacy with applications in the private and public sectors. Most of the techniques that achieve differential privacy are based on a judicious use of randomness. However, reasoning about randomized programs is difficult and error prone. For this reason, several techniques have been recently proposed to support designer in proving programs differentially private or in finding violations to it.

In this work we propose a technique based on symbolic execution for reasoning about differential privacy. Symbolic execution is a classic technique used for testing, counterexample generation and to prove absence of bugs. Here we use symbolic execution to support these tasks specifically for differential privacy. To achieve this goal, we design a relational symbolic execution technique which supports reasoning about probabilistic coupling, a formal notion that has been shown useful to structure proofs of differential privacy. We show how our technique can be used to both verify and find violations to differential privacy.
Relativistic impulse approximation in the atomic ionization process induced by millicharged particles
Authors: Qiao Chen-Kai , Lin Shin-Ted , Chi Hsin-Chang , Jia Hai-Tao
Published: March 2021

Abstract

The millicharged particle has become an attractive topic to probe physics beyond the Standard Model. In direct detection experiments, the parameter space of millicharged particles can be constrained from the atomic ionization process. In this work, we develop the relativistic impulse approximation (RIA) approach, which can duel with atomic many-body effects effectively, in the atomic ionization process induced by millicharged particles. The formulation of RIA in the atomic ionization induced by millicharged particles is derived, and the numerical calculations are obtained and compared with those from free electron approximation and equivalent photon approximation. Concretely, the atomic ionizations induced by mllicharged dark matter particles and millicharged neutrinos in high-purity germanium (HPGe) and liquid xenon (LXe) detectors are carefully studied in this work. The differential cross sections, reaction event rates in HPGe and LXe detectors, and detecting sensitivities on dark matter particle and neutrino millicharge in next-generation HPGe and LXe based experiments are estimated and calculated to give a comprehensive study. Our results suggested that the next-generation experiments would improve 2-3 orders of magnitude on dark matter particle millicharge δχ than the current best experimental bounds in direct detection experiments. Furthermore, the next-generation experiments would also improve 2-3 times on neutrino millicharge δν than the current experimental bounds.
The physics potential of a reactor neutrino experiment with Skipper CCDs: measuring the weak mixing angle
Authors: Fernandez-Moroni Guillermo , Machado Pedro A. N. , Martinez-Soler Ivan , Perez-Gonzalez Yuber F. , Rodrigues Dario , Rosauro-Alcaraz Salvador
Published: March 2021

Abstract

We analyze in detail the physics potential of an experiment like the one recently proposed by the vIOLETA collaboration: a kilogram-scale Skipper CCD detector deployed 12 meters away from a commercial nuclear reactor core. This experiment would be able to detect coherent elastic neutrino nucleus scattering from reactor neutrinos, capitalizing on the exceptionally low ionization energy threshold of Skipper CCDs. To estimate the physics reach, we elect the measurement of the weak mixing angle as a case study. We choose a realistic benchmark experimental setup and perform variations on this benchmark to understand the role of quenching factor and its systematic uncertainties, background rate and spectral shape, total exposure, and reactor antineutrino flux uncertainty. We take full advantage of the reactor flux measurement of the Daya Bay collaboration to perform a data driven analysis which is, up to a certain extent, independent of the theoretical un- certainties on the reactor antineutrino flux. We show that, under reasonable assumptions, this experimental setup may provide a competitive measurement of the weak mixing angle at few MeV scale with neutrino-nucleus scattering.
Condensates and anomaly cascade in vector-like theories
Authors: Anber Mohamed M.
Published: March 2021

Abstract

We study the bilinear and higher-order fermion condensates in 4-dimensional SU(N) gauge theories with a single Dirac fermion in a general representation. Augmented with a mixed anomaly between the 0-form discrete chiral, 1-form center, and 0-form baryon number symmetries (BC anomaly), we sort out theories that admit higher-order condensates and vanishing fermion bilinears. Then, the BC anomaly is utilized to prove, in the absence of a topological quantum field theory, that nonvanishing fermion bilinears are inevitable in infrared-gapped theories with 2-index (anti)symmetric fermions. We also contrast the BC anomaly with the 0-form anomalies and show that it is the former anomaly that determines the infrared physics; we argue that the BC anomaly lurks deep to the infrared while the 0-form anomalies are just variations of local terms. We provide evidence of this assertion by studying the BC anomaly in vector-like theories compactified on a small spacial circle. These theories are weakly-coupled, under analytical control, and they admit a dual description in terms of abelian photons that determine the deep infrared dynamics. We show that the dual photons talk directly to the 1-form center symmetry in order to match the BC anomaly, while the 0-form anomalies are variations of local terms and are matched by fiat. Finally, we study the fate of the BC anomaly in the compactified theories when they are held at a finite temperature. The effective field theory that describes the low-energy physics is 2-dimensional. We show that the BC anomaly cascades from 4 to 2 dimensions.
String theory and the arrow of time
Authors: Itzhaki Nissan
Published: March 2021

Abstract

Time-like linear dilaton triggers, at the classical level, the creation of closed folded strings at an instant. We show that in cosmology these instant folded strings induce negative pressure at no energy cost. Hence they seem to allow an era in which the energy density increases (decreases) while the universe is expanding (contracting). This and other aspects of instant folded strings suggest that they might shed new light on the origin of the arrow of time.
Blunt popliteal artery injury following tibiofemoral trauma: vessel-first and bone-first strategy
Authors: Hundersmarck Dennis , Hietbrink Falco , Leenen Luke P. H. , De Borst Gert J. , Heng Marilyn
Published: March 2021

Purpose

Blunt popliteal artery injury (BPAI) is a potentially limb-threatening sequela of tibiofemoral (knee) dislocations and fractures. Associated amputation rates for all popliteal artery (PA) injuries range between 10 and 50%. It is unclear whether PA repair or bone stabilization should be performed first. We analyzed (long-term) clinical outcomes of BPAI patients that received initial PA repair (vessel-first, VF) versus initial external stabilization (bone-first, BF).

Methods

Retrospectively, all surgically treated BPAI patients between January 2000 and January 2019, admitted to two level 1 trauma centers were included. Clinical outcomes were determined, stratified by initial management strategy (VF and BF). Treatment strategy was determined by surgeon preference, based on associated injuries and ischemia duration. Primary outcomes (amputation and mortality) and secondary outcomes (claudication and complications) were determined.

Results

Of 27 included BPAI patients, 15 were treated according to the VF strategy (56%) and 12 according to the BF strategy (44%). Occlusion was the most frequently encountered BPAI in 18/27 patients (67%). Total delay and in-hospital delay were comparable between groups (p = 1.00 and p = 0.82). Revascularization was most frequently performed by PA bypass (59%). All patients had primary limb salvage during admission (100%). One secondary amputation due to knee pain was performed in the BF group (4%). During a median clinical follow-up period of 2.7 years, three PA re-interventions were performed, two in the BF group and one in the VF group. None suffered from (intermittent) claudication.

Conclusion

Blunt popliteal artery injury (BPAI) is a rare surgical emergency. Long-term outcomes of early revascularization for BPAI appear to be good, independent of initial management strategy. The BF strategy may be preferred in case of severe orthopedic injury, if allowed by total ischemia duration.
Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta
Authors: Malmgren Barbro , Thesleff Irma , Dahllöf Göran , Åström Eva , Tsilingaridis Georgios
Published: March 2021

Treatment with intravenous bisphosphonate (BP) in children and adolescents with osteogenesis imperfecta (OI) started in Sweden in 1991. No human studies on the role of BP therapy in development of disturbances in tooth mineralization or tooth morphology have been published. The study cohort comprised 219 individuals who were divided into four groups: group 1, BP treatment onset before 2 years of age (n = 22); group 2, BP treatment onset between 2 and 6 years of age (n = 20); group 3, BP treatment onset between 6 and 10 years of age (n = 13); and a control group of patients with OI who had not received BP therapy (n = 164). The chi-square test was used in between-group comparisons of the prevalence of tooth agenesis. The prevalence of tooth agenesis was significantly higher in children who began BP treatment before the age of 2 years (group 1; 59%,) compared to the controls (10%; p < 0.001) and to children who had begun BP therapy between ages 2 and 6 years (group 2; 10%; p = 0.009) or between ages 6 and 10 years (group 3; 8%; p = 0.003). Different types of disturbances in the enamel formation were seen in 52 premolars, where 51 were seen in those who began BP treatment before the age of 2 years. To conclude, starting BP treatment before the age of 2 years increases the risk of abnormalities in tooth formation manifesting as morphological aberrations, tooth agenesis, and enamel defects.
The association between alcohol consumption and osteoarthritis: a meta-analysis and meta-regression of observational studies
Authors: To Kendrick , Mak Christopher , Zhang Chen , Zhou Yuhui , Filbay Stephanie , Khan Wasim
Published: March 2021

There is conflicting evidence for the association between alcohol consumption and common joint conditions such as Osteoarthritis (OA), which affects millions of people. We sought to determine the true association between alcohol intake and OA. We conducted a PRISMA systematic review and meta-analysis of observational studies that reported associations between alcohol consumption and OA. Pooled estimates of association were represented through odds ratios (ORs). Publication bias was assessed with Funnel and Galbraith plots, and risk of bias was assessed with the Newcastle Ottawa Scale. We included 29 studies and 25,192 subjects with OA and reported an OR between any alcohol consumption and OA of 0.79 (0.68–0.93), suggesting a protective effect. OR of weekly or more frequent use was 0.79 (0.65–0.97). When grouped by covariates, alcohol consumption was negatively associated with radiographic (0.83, 0.70–0.98), hand (0.80, 0.66–0.95) and knee OA (0.85, 0.72–0.99), North American ethnicity and female gender. Subgroup analysis of unadjusted data resulted in an OR of 0.70 (0.55–0.89) but this disappeared upon analysis of studies with data adjusted for any covariate (0.93, 0.78–1.10). Whilst our pooled analysis suggest that weekly or more frequent alcohol consumption was negatively associated with OA, this was not observed when adjusted for confounding factors. Reasons for this include selection bias and lack of longitudinal exposure and adjustment for confounding variables. Therefore, this meta-analysis provides evidence to dispel notions that alcohol use may be protective against OA.
Prognostic value of the chest X-ray in patients hospitalised for heart failure
Authors: Pan Daniel , Pellicori Pierpaolo , Dobbs Karen , Bulemfu Jeanne , Sokoreli Ioanna , Urbinati Alessia , Brown Oliver , Sze Shirley , Rigby Alan S. , Kazmi Syed , Riistama Jarno M. , Cleland John G. F. , Clark Andrew L.
Published: March 2021

Background

Patients admitted to hospital with heart failure will have had a chest X-ray (CXR), but little is known about their prognostic significance. We aimed to report the prevalence and prognostic value of the initial chest radiograph findings in patients admitted to hospital with heart failure (acute heart failure, AHF).

Methods

The erect CXRs of all patients admitted with AHF between October 2012 and November 2016 were reviewed for pulmonary venous congestion, Kerley B lines, pleural effusions and alveolar oedema. Film projection (whether anterior–posterior [AP] or posterior–anterior [PA]) and cardiothoracic ratio (CTR) were also recorded. Trial registration: ISRCTN96643197

Results

Of 1145 patients enrolled, 975 [median (interquartile range) age 77 (68–83) years, 61% with moderate, or worse, left ventricular systolic dysfunction, and median NT-proBNP 5047 (2337–10,945) ng/l] had an adequate initial radiograph, of which 691 (71%) were AP. The median CTR was 0.57 (IQR 0.53–0.61) in PA films and 0.60 (0.55–0.64) in AP films. Pulmonary venous congestion was present in 756 (78%) of films, Kerley B lines in 688 (71%), pleural effusions in 649 (67%) and alveolar oedema in 622 (64%).

A CXR score was constructed using the above features. Increasing score was associated with increasing age, urea, NT-proBNP, and decreasing systolic blood pressure, haemoglobin and albumin; and with all-cause mortality on multivariable analysis (hazard ratio 1.10, 95% confidence intervals 1.07–1.13, p < 0.001).

Conclusions

Radiographic evidence of congestion on a CXR is very common in patients with AHF and is associated with other clinical measures of worse prognosis.

Graphic abstract
The effect of biofeedback interventions on pain, overall symptoms, quality of life and physiological parameters in patients with pelvic pain
Authors: Wagner Barbara , Steiner Margarete , Huber Dominikus Franz Xaver , Crevenna Richard
Published: March 2021

Background

Biofeedback is recognized as an effective additive method for treating certain phenotypes of chronic pelvic pain syndrome and is a therapeutic option in other pelvic pain conditions. This review aims to evaluate evidence from the literature with a focus on the effect of biofeedback on pain reduction, overall symptom relief, physiological parameters and quality of life.

Methods

A systematic literature search was conducted using the databases PubMed, MEDLINE, Embase, Cochrane Library and PEDro from inception to July 2020. Data were tabulated and a narrative synthesis was carried out, since data heterogeneity did not allow a meta-analysis. The PEDro scale and the McMaster Critical Review Form—Quantitative Studies were applied to assess risk of bias.

Results

Out of 651 studies, 37 quantitative studies of primary research evaluating pelvic pain conditions in male and female adults and children were included. They covered biofeedback interventions on anorectal disorders, chronic prostatitis, female chronic pelvic pain conditions, urologic phenotypes in children and adults and a single study on low back pain. For anorectal disorders, several landmark studies demonstrate the efficacy of biofeedback. For other subtypes of chronic pelvic pain conditions there is tentative evidence that biofeedback-assisted training has a positive effect on pain reduction, overall symptoms relief and quality of life. Certain factors have been identified that might be relevant in improving treatment success.

Conclusions

For certain indications, biofeedback has been confirmed to be an effective treatment. For other phenotypes, promising findings should be further investigated in robust and well-designed randomized controlled trials.
Overview of the contemporary management of supracondylar humeral fractures in children
Authors: Duffy Sean , Flannery Oliver , Gelfer Yael , Monsell Fergal
Published: March 2021

Purpose

Supracondylar fractures are common injuries accounting for approximately 15% of all fractures in children with a large body of literature on this subject.

Methods

 This article critically appraises the available evidence to provide an overview of the treatment options including the role and timing of surgery, the geometry of wire fixation and the management of nerve and arterial injury.

Conclusion

 Management decisions are based on a number of considerations particularly fracture stability. Closed reduction and percutaneous K-wire stabilisation are commonly recommended for an unstable displaced fracture. These techniques are however associated with the potential for iatrogenic neurological injury. Vascular injury is also rare but must be recognised and treated promptly to avoid significant permanent morbidity.
Development of a hollow fibre-based renal module for active transport studies
Authors: Englezakis Alexandros , Gozalpour Elnaz , Kamran Mohammed , Fenner Katherine , Mele Elisa , Coopman Karen
Published: March 2021

Understanding the active transport of substrates by the kidney in the renal proximal convoluted tubule is crucial for drug development and for studying kidney diseases. Currently, cell-based assays are applied for this this purpose, however, differences between assays and the body are common, indicating the importance of in vitro–in vivo discrepancies. Several studies have suggested that 3D cell cultures expose cells to a more physiological environments, thus, providing more accurate cell function results. To mimic the renal proximal tubule, we have developed a custom-made renal module (RM), containing a single polypropylene hollow fibre (Plasmaphan P1LX, 3M) that serves as a porous scaffold and compared to conventional Transwell cell-based bidirectional transport studies. In addition, a constant flow of media, exposed cells to a physiological shear stress of 0.2 dyne/cm2. MDCK-Mdr1a cells, overexpressing the rat Mdr1a (P-gp) transporter, were seeded onto the HF membrane surface coated with the basement membrane matrix Geltrex which facilitated cell adhesion and tight junction formation. Cells were then seeded into the HF lumen where attachment and tight junction formation were evaluated by fluorescence microscopy while epithelial barrier integrity under shear stress was shown to be achieved by day 7. qPCR results have shown significant changes in gene expression compared to cells grown on Transwells. Kidney injury marker such as KIM-1 and the hypoxia marker CA9 have been downregulated, while the CD133 (Prominin-1) microvilli marker has shown a fivefold upregulation. Furthermore, the renal transporter P-gp expression has been downregulated by 50%. Finally, bidirectional assays have shown that cells grown in the RM were able to reabsorb albumin with a higher efficiency compared to Transwell cell cultures while efflux of the P-gp-specific substrates Hoechst and Rhodamine 123 was decreased. These results further support the effect of the microenvironment and fluidic shear stress on cell function and gene expression. This can serve as the basis for the development of a microphysiological renal model for drug transport studies.
Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab
Authors: Boku Narikazu , Satoh Taroh , Ryu Min-Hee , Chao Yee , Kato Ken , Chung Hyun Cheol , Chen Jen-Shi , Muro Kei , Kang Won Ki , Yeh Kun-Huei , Yoshikawa Takaki , Oh Sang Cheul , Bai Li-Yuan , Tamura Takao , Lee Keun-Wook , Hamamoto Yasuo , Kim Jong Gwang , Chin Keisho , Oh Do-Youn , Minashi Keiko , Cho Jae Yong , Tsuda Masahiro , Nishiyama Taihei , Chen Li-Tzong , Kang Yoon-Koo
Published: March 2021

Background

ATTRACTION-2 demonstrated that nivolumab improved overall survival (OS) vs placebo in patients with advanced gastric cancer treated with ≥ 2 chemotherapy regimens. However, its long-term efficacy and outcome of treatment beyond progression (TBP) with nivolumab have not been clarified.

Methods

The 3-year follow-up data were collected. A subset analysis was performed to explore the efficacy of TBP by assessing postprogression survival (PPS) after the first event of disease progression.

Results

Overall, 493 patients were randomized (2:1) to receive nivolumab (n = 330) or placebo (n = 163). With a median follow-up of 38.5 (range 36.1–47.5) months, OS of the nivolumab group was significantly longer compared to the placebo group (median 5.3 vs 4.1 months; 3-year survival rate, 5.6% vs 1.9%; hazard ratio [HR], 0.62 [95% confidence interval (CI) 0.50–0.75], P < 0.0001). The median OS of responders (n = 32) who achieved complete response or partial response was 26.7 months and the 3-year survival rate was 35.5% in the nivolumab group. Overall, 109 patients in the nivolumab group and 37 patients in the placebo group received TBP. PPS tended to be longer in the nivolumab group vs placebo group (median 5.8 vs 4.5 months; HR [95% CI], 0.69 [0.47–1.01], P = 0.057). In contrast, PPS was similar between both treatment groups in non-TBP patients (median 2.3 vs 2.2 months; HR 0.90, P = 0.42).

Conclusions

Long-term efficacy of nivolumab was confirmed at the 3-year follow-up, and a survival benefit of TBP with nivolumab was suggested. Biomarkers for selecting patients suitable for TBP with nivolumab should be identified in the future.
Trust me; I know what I am doing investigating the effect of choice list elicitation and domain-relevant training on preference reversals in decision making for others
Authors: Neumann-Böhme Sebastian , Lipman Stefan A. , Brouwer Werner B. F. , Attema Arthur E.
Published: March 2021

One core assumption of standard economic theory is that an individual’s preferences are stable, irrespective of the method used to elicit them. This assumption may be violated if preference reversals are observed when comparing different methods to elicit people’s preferences. People may then prefer A over B using one method while preferring B over A using another. Such preference reversals pose a significant problem for theoretical and applied research. We used a sample of medical and economics students to investigate preference reversals in the health and financial domain when choosing patients/clients. We explored whether preference reversals are associated with domain-relevant training and tested whether using guided ‘choice list’ elicitation reduces reversals. Our findings suggest that preference reversals were more likely to occur for medical students, within the health domain, and for open-ended valuation questions. Familiarity with a domain reduced the likelihood of preference reversals in that domain. Although preference reversals occur less frequently within specialist domains, they remain a significant theoretical and practical problem. The use of clearer valuation procedures offers a promising approach to reduce preference reversals.
Media consumption and mental health during COVID-19 lockdown: a UK cross-sectional study across England, Wales, Scotland and Northern Ireland
Authors: Neill Ruth D , Blair Carolyn , Best Paul , McGlinchey Emily , Armour Cherie
Published: March 2021

Aim

As individuals adjust to new ‘norms’ and ways of living during the COVID-19 lockdown, there is a continuing need for up-to-date information and guidance. Evidence suggests that frequent media exposure is related to a higher prevalence of mental health problems, especially anxiety and depression. The aim of this study was to determine whether COVID-19 related media consumption is associated with changes in mental health outcomes.

Methods

This paper presents baseline data from the COVID-19 Psychological Wellbeing Study. The cross-sectional study data was collected using an online survey following the Generalised Anxiety Disorder scale (GAD-7) and the Patient Health Questionnaire (PHQ-9), with some other basic information collected. Logistic regression analysis was used to examine the influence of socio-demographic and media specific factors on anxiety and depression.

Results

The study suggested that media usage is statistically significantly associated with anxiety and depression on the GAD-7 and PHQ-9 scales with excessive media exposure related to higher anxiety and depression scores.

Conclusion

This study indicated that higher media consumption was associated with higher levels of anxiety and depression. Worldwide it should be acknowledged that excessive media consumption, particularly social media relating to COVID-19, can have an effect on mental health. However, as this was a cross-sectional study we cannot infer any directionality as we cannot infer cause and effect; therefore, future research involving longitudinal data collection and analyses of variables over time is warranted.
Exploring digital image correlation technique for the analysis of the tensile properties of all-cellulose composites
Authors: Chen Feng , Bouvard Jean-Luc , Sawada Daisuke , Pradille Christophe , Hummel Michael , Sixta Herbert , Budtova Tatiana
Published: March 2021

All-cellulose composites (ACCs) were prepared from filter paper via partial dissolution in the ionic liquid 1-ethyl-3-methylimidazolium acetate, and material tensile properties were investigated using various approaches. One is based on data directly taken from a tensile testing machine, and the other uses two-cameras stereovision with digital image correlation (DIC) technique. In the latter case, virtual extensometer with different locations on the sample and averaging over sample surface were tested. Nominal and true stress–strain dependences were built and Young's modulus, tensile strength, elongation at maximal stress and toughness were evaluated as a function of ACC density. A minor difference was observed for the stress–strain dependences derived from different approaches which use the DIC technique, most probably because of low ACC deformation. However, the results reveal that the nominal stress–strain curve from DIC is significantly different from that which is directly derived from the data provided by machine sensors thus strongly impacting Young’s modulus and elongation at break values. This study provides an insight into the evaluation of the mechanical properties of ACCs.

Graphic abstract
Beyond one-way determinism: San Frediano’s miracle and climate change in Central and Northern Italy in late antiquity
Authors: Zanchetta Giovanni , Bini Monica , Bloomfield Kevin , Izdebski Adam , Vivoli Nicola , Regattieri Eleonora , Isola Ilaria , Drysdale Russell N. , Bajo Petra , Hellstrom John C. , Wiśniewski Robert , Fallick Anthony E. , Natali Stefano , Luppichini Marco
Published: March 2021

Integrating palaeoclimatological proxies and historical records, which is necessary to achieve a more complete understanding of climate impacts on past societies, is a challenging task, often leading to unsatisfactory and even contradictory conclusions. This has until recently been the case for Italy, the heart of the Roman Empire, during the transition between Antiquity and the Middle Ages. In this paper, we present new high-resolution speleothem data from the Apuan Alps (Central Italy). The data document a period of very wet conditions in the sixth c. AD, probably related to synoptic atmospheric conditions similar to a negative phase of the North Atlantic Oscillation. For this century, there also exist a significant number of historical records of extreme hydroclimatic events, previously discarded as anecdotal. We show that this varied evidence reflects the increased frequency of floods and extreme rainfall events in Central and Northern Italy at the time. Moreover, we also show that these unusual hydroclimatic conditions overlapped with the increased presence of “water miracles” in Italian hagiographical accounts and social imagination. The miracles, performed by local Church leaders, strengthened the already growing authority of holy bishops and monks in Italian society during the crucial centuries that followed the “Fall of the Roman Empire”. Thus, the combination of natural and historical data allows us to show the degree to which the impact of climate variability on historical societies is determined not by the nature of the climatic phenomena per se, but by the culture and the structure of the society that experienced it.
Whose Life is it Anyway? Exploring the Social Relations of High-Conflict Divorce Cases in Southern Norway
Authors: Bertelsen Bård
Published: March 2021

The paper reports on findings from an empirical study based on qualitative interviews with Norwegian parents identified as part of a high-conflict divorce situation and interviews with caseworkers from a child welfare service. The site of study is an institutional circuit of concern, assessment, and referral involving the court, child welfare services, and a public family therapy service. The paper draws on the social ontology and analytic concepts of institutional ethnography and adopts parents’ standpoint to explore how their knowledge and experience are shaped through encounters with professionals in the process of being identified and assessed as a high-conflict divorce case. The focus on people’s doings and their expert knowledge about their doings sets institutional ethnographic research apart from more conventional forms of qualitative inquiry that focus on informants’ inner experience. The paper highlights how a generalized professional discourse seems to permeate the work that parents and caseworkers jointly engage in, sometimes subsuming the knowledge and experience of those involved. When the issues of life as subjectively known and experienced are different from those of the institutional discourse, there is a danger that what is important to those whose lives they concern escapes the dialogue between parents and professionals.
Does the Association Between Flows of People and Crime Differ Across Crime Types in Sweden?
Authors: Gerell Manne
Published: March 2021

Places with persistently high levels of crime, hot spots, are an important object of study. To some extent, the high levels of crime at such hot spots are likely to be related to flows of people. City center locations with large flows of people are quite often also hot spots, e.g., hot spots for pick pocketing at a central train station, or hot spots for assault in the nightlife district. This can be related to crime pattern theory, or to the routine activity perspective, which both suggest that flows of people can affect crime. The present study attempts to explore and quantify whether there are differences in the association between flows of people and crime for different crime types. The analysis considers locations with high crime counts for six crime types in the city of Malmö, Sweden. For each crime type, hot spots are identified and mapped, and in order to explore whether, or how, these are related to flows of people, the crime levels are then analyzed in relation to the number of people who boarded a local bus (N = 33,134,198) nearby. The paper shows that all six crime types are associated with flows of people, although less so for arson and vandalism. This is hypothesized to be due to the relatively constant target availability for these crimes as opposed to the other crime types studied.
The electrophysiological tests in the early detection of the visual pathway dysfunction in patients with microadenoma
Authors: Lachowicz Ewelina , Lubiński Wojciech , Gosławski Wojciech , Andrysiak-Mamos Elżbieta , Kaźmierczyk-Puchalska Agnieszka , Syrenicz Anhelli
Published: March 2021

Purpose

To evaluate the validity of electrophysiological tests in the early diagnosis of a ganglion cells and/or optic nerve dysfunction in patients with pituitary microadenoma.

Methods

66 eyes, from 33 patients with microadenoma with no evidence of the optic chiasm compression in magnetic resonance imaging (MRI) and the visual impairment in the routine ophthalmological examination, standard static perimetry (24-2 white on white) and optical coherence tomography (HD-OCT), were analysed. The pattern electroretinogram (PERG), standard pattern visual evoked potentials (PVEPs) and multichannel visual evoked potentials (mVEPs) (ISCEV standards) were performed. The results obtained from the electrophysiological tests were compared to the same number of age-matched healthy controls.

Results

Statistically significant differences between the patients with microadenoma and healthy controls were detected in all electrophysiological tests (p < 0.001). The most frequent abnormalities were observed in mVEPs (25/33 patients, 75.8%; 43/66 eyes, 65.2%). The most frequent features registered in this test were: (1°4′)—an increase in the P100wave latency from uncrossed fibres (13/33 patients, 39.39%; 21/66 eyes, 31.8%) and (0°16′)—an amplitude reduction of this wave from the crossed fibres (11/33 patients, 33.33%; 19/66 eyes, 28.8%). The changes in PVEPs (15/33 patients, 45.5%; 25/66 eyes, 37.9%) and PERG (10/33 patients, 30.3%; 15/66 eyes, 22.7%) were also registered. Of all the tests and parameters analysed in the study, the greatest diagnostic value in detecting the visual pathway dysfunction in this group of patients was the amplitude of P100 wave from the crossed fibres of the mVEPs (1°4′) with a sensitivity of 60.6% and a specificity of 93.8%. These parameters suggest that this type of dysfunction is downstream to the chiasm and can also indicate the visual pathway dysfunction severity.

Conclusions

In patients with microadenoma, the abnormalities in the electrophysiological tests are registered even without clinical evidence of visual impairment from the routine ophthalmological examination, SAP, OCT and chiasmal compression in MRI. The mVEPs have the most significant role in the diagnosis of the visual pathway dysfunction in patients with microadenoma.
Effect of severe renal impairment on the pharmacokinetics of brigatinib
Authors: Gupta Neeraj , Hanley Michael J. , Kerstein David , Tugnait Meera , Narasimhan Narayana , Marbury Thomas C. , Venkatakrishnan Karthik
Published: March 2021

Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigatinib is approved in multiple countries for treatment of patients with ALK-positive non–small cell lung cancer. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is required for patients with mild or moderate renal impairment. Methods An open-label, single-dose study was conducted to evaluate the PK of brigatinib (90 mg) in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2; n = 8) and matched healthy volunteers with normal renal function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2; n = 8). Plasma and urine were collected for the determination of plasma protein binding and estimation of plasma and urine PK parameters. Results Plasma protein binding of brigatinib was similar between patients with severe renal impairment (92 % bound) and matched healthy volunteers with normal renal function (91 % bound). Unbound brigatinib exposure (area under the plasma concentration-time curve from time zero to infinity) was approximately 92 % higher in patients with severe renal impairment compared with healthy volunteers with normal renal function. The renal clearance of brigatinib in patients with severe renal impairment was approximately 20 % of that observed in volunteers with normal renal function. Conclusions These findings support a brigatinib dosage reduction of approximately 50 % in patients with severe renal impairment.

Trial registry: Not applicable.
Comparing effectiveness, cost- and time-efficiency of control options for Xanthomonas wilt of banana under Rwandan agro-ecological conditions
Authors: Blomme Guy , Dusingizimana Petronille , Ntamwira Jules , Kearsley Elizabeth , Gaidashova Svetlana , Rietveld Anne , Van Schagen Boudy , Ocimati Walter
Published: March 2021

Xanthomonas wilt of banana (XW) is a major disease affecting banana throughout East and Central Africa (ECA). Initial control was through complete diseased mat uprooting (CDMU), which had limited adoption due to high labour demands and cost. Further research demonstrated single diseased stem removal (SDSR) was an effective, less labour intensive and less costly alternative to CDMU. A comparative assessment of the two control practices was needed to foster uptake by policy makers, especially in countries like Rwanda where SDSR had not been tested or scaled up. To test SDSR in Rwanda, a study was conducted in farmers’ fields comparing the effectiveness, labour cost and time demands of CDMU and SDSR. SDSR was equally effective as CDMU for XW control, with initial XW incidences of 3.0 to 9.4% being reduced to <0.5% within 3 months of using either method. The major benefit of SDSR lies in its significantly lower resource requirements. The total time needed for applying SDSR on a single plant was 88% less, averaging 4.3 min (standard deviation, sd = 0.3) compared to 36.5 min (sd = 4.5) for CDMU on a complete mat. Accordingly, the cost of labour was significantly lower for SDSR. The main cost of CDMU (78% of total cost) arose from the need to replant with healthy banana plantlets. The total cost of SDSR (26 Rwandan Francs [Frw], sd = 2) was 96% lower than that for CDMU (619 Frw, sd = 27). Hence, the incentive to use SDSR for managing XW is very high. These findings will boost SDSR adoption by both policy makers and farmers in ECA.
John Rawls and compliance to climate change agreements: insights from a laboratory experiment
Authors: Klaser Klaudijo , Sacconi Lorenzo , Faillo Marco
Published: March 2021

The most evident shortcoming of the international agreements on climate actions is the compliance to their prescriptions. Can John Rawls’s social contract theory help us to solve the problem? We apply the veil of ignorance decision-making setting in a sequential dictator game to study the compliance to climate change agreements and we test the model in a laboratory experiment. The veil of ignorance shows to be very powerful at inducing the subjects to converge on a sustainable intergenerational path. However, the voluntary compliance to the agreement still remains an open issue, because even small incentives to defect can undermine the compliance stability, and therefore break the whole sustainable dynamic.
Examining the impact of socioeconomic variables on COVID-19 death rates at the state level
Authors: Doti James L.
Published: March 2021

This study uses a step-wise regression model to identify the socioeconomic variables most significant in explaining COVID-19 death rates on a state-level basis. The regression tests cover the 1/1/2020 to 12/1/2020 period as well as the first and second halves of 2020. This study also uses the Oxford stringency index to measure more precisely the efficacy of governmental mandates at the state level. The results in this study rigorously showed that while the density variables were the most significant explanatory variables during the first half of the year, their significance fell during the second half. Use of the Oxford stringency index revealed that more stringent mandates led to significant reductions in COVID-19 death rates, especially during the second half of the year. The study’s findings also reveal that a higher poverty rate in a state is significantly associated with higher COVID-19 death rates during all three periods tested.
The corticospinal tract structure of collagen/silk fibroin scaffold implants using 3D printing promotes functional recovery after complete spinal cord transection in rats
Authors: Li Xiao-Hong , Zhu Xiang , Liu Xiao-Yin , Xu Hai-Huan , Jiang Wei , Wang Jing-Jing , Chen Feng , Zhang Sai , Li Rui-Xin , Chen Xu-Yi , Tu Yue
Published: March 2021

No effective treatment has been established for nerve dysfunction caused by spinal cord injury (SCI). Orderly axonal growth at the site of spinal cord transection and creation of an appropriate biological microenvironment are important for functional recovery. To axially guiding axonal growth, designing a collagen/silk fibroin scaffold fabricated with 3D printing technology (3D-C/SF) emulated the corticospinal tract. The normal collagen/silk fibroin scaffold with freeze-drying technology (C/SF) or 3D-C/SF scaffold were implanted into rats with completely transected SCI to evaluate its effect on nerve repair during an 8-week observation period. Electrophysiological analysis and locomotor performance showed that the 3D-C/SF implants contributed to significant improvements in the neurogolical function of rats compared to C/SF group. By magnetic resonance imaging, 3D-C/SF implants promoted a striking degree of axonal regeneration and connection between the proximal and distal SCI sites. Compared with C/SF group, rats with 3D-C/SF scaffold exhibited fewer lesions and disordered structures in histological analysis and more GAP43-positive profiles at the lesion site. The above results indicated that the corticospinal tract structure of 3D printing collagen/silk fibroin scaffold improved axonal regeneration and promoted orderly connections within the neural network, which could provided a promising and innovative approach for tissue repair after SCI.
Continuous non‐contact respiratory rate and tidal volume monitoring using a Depth Sensing Camera
Authors: Addison Paul S. , Smit Philip , Jacquel Dominique , Addison Anthony P. , Miller Cyndy , Kimm Gardner
Published: March 2021

The monitoring of respiratory parameters is important across many areas of care within the hospital. Here we report on the performance of a depth-sensing camera system for the continuous non-contact monitoring of Respiratory Rate (RR) and Tidal Volume (TV), where these parameters were compared to a ventilator reference. Depth sensing data streams were acquired and processed over a series of runs on a single volunteer comprising a range of respiratory rates and tidal volumes to generate depth-based respiratory rate (RRdepth) and tidal volume (TVdepth) estimates. The bias and root mean squared difference (RMSD) accuracy between RRdepth and the ventilator reference, RRvent, across the whole data set was found to be -0.02 breaths/min and 0.51 breaths/min respectively. The least squares fit regression equation was determined to be: RRdepth = 0.96 × RRvent + 0.57 breaths/min and the resulting Pearson correlation coefficient, R, was 0.98 (p < 0.001). Correspondingly, the bias and root mean squared difference (RMSD) accuracy between TVdepth and the reference TVvent across the whole data set was found to be − 0.21 L and 0.23 L respectively. The least squares fit regression equation was determined to be: TVdepth = 0.79 × TVvent—0.01 L and the resulting Pearson correlation coefficient, R, was 0.92 (p < 0.001). In conclusion, a high degree of agreement was found between the depth-based respiration rate and its ventilator reference, indicating that RRdepth is a promising modality for the accurate non-contact respiratory rate monitoring in the clinical setting. In addition, a high degree of correlation between depth-based tidal volume and its ventilator reference was found, indicating that TVdepth may provide a useful monitor of tidal volume trending in practice. Future work should aim to further test these parameters in the clinical setting.
Polyhedral approximation strategies for nonconvex mixed-integer nonlinear programming in SHOT
Authors: Lundell Andreas , Kronqvist Jan
Published: March 2021

Different versions of polyhedral outer approximation are used by many algorithms for mixed-integer nonlinear programming (MINLP). While it has been demonstrated that such methods work well for convex MINLP, extending them to solve nonconvex problems has traditionally been challenging. The Supporting Hyperplane Optimization Toolkit (SHOT) is a solver based on polyhedral approximations of the nonlinear feasible set of MINLP problems. SHOT is an open source COIN-OR project, and is currently one of the most efficient global solvers for convex MINLP. In this paper, we discuss some extensions to SHOT that significantly extend its applicability to nonconvex problems. The functionality include utilizing convexity detection for selecting the nonlinearities to linearize, lifting reformulations for special classes of functions, feasibility relaxations for infeasible subproblems and adding objective cuts to force the search for better feasible solutions. This functionality is not unique to SHOT, but can be implemented in other similar methods as well. In addition to discussing the new nonconvex functionality of SHOT, an extensive benchmark of deterministic solvers for nonconvex MINLP is performed that provides a snapshot of the current state of nonconvex MINLP.
Oxidation-Enhanced Evaporation in High-Carbon Ferromanganese
Authors: Myklebust Håkon Aleksander Hartvedt Olsen , Andersson Stefan , Tranell Gabriella
Published: March 2021

Thermal fume formation is a problem in manganese ferroalloy production and the metal production industry at large. A better understanding of the mechanisms of fume formation and the operational parameters affecting the fume formation rate may help in reducing and managing fuming. This paper aims to investigate the effects of oxygen content and gas flow rate on the fuming rate and fume particulate properties for liquid high-carbon ferromanganese. The fuming rates were attained experimentally by measuring the fume flux with respect to oxygen content and gas velocity above the metal melt. The generated fumes were also characterized in terms of particle size and element distribution between fume and melt. The fuming rates were found to steadily increase with increasing oxygen content and flow rate of the gas up to a point where the curve flattens, following theoretical predictions. However, the highest flux values measured were above the theoretical limitations of the evaporation flux in vacuo given the alloy bulk composition. It is hypothesized that the high rate of fuming is caused by an increased manganese activity at the alloy surface due to local decarburization of the alloy in contact with the oxidizing gas.

Graphical Abstract