bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper urinary tract function of patients with multiple sclerosis
Authors: Piquet Violaine , Turmel Nicolas , Chesnel Camille , Haddad Rebecca , Lebreton Frédérique , Amarenco Gérard , Hentzen Claire
Published: December 2021

Background

Neurogenic lower urinary tract dysfunction (NLUTD) is frequent in multiple sclerosis (MS) and renal prognosis is a key point of bladder management.

Objective

To assess upper urinary tract damage risk using voiding cystourethrography (VCUG) in patients with (PwMS) and NLUTD.

Methods

We conducted a retrospective study between 2010 and 2020. Demographic data, urinary symptoms, urinary tract infection (UTI), renal ultrasounds findings, glomerular filtration rate (GFR), VCUG data, and urodynamic parameters were collected in PwMS with NLUTD.

Results

Among 325 PwMS included, 67% were female, mean age was 51.6 ± 12.0 years, and mean EDSS 4.6 ± 1.8. VCUG showed vesicoureteral reflux (VUR) in 18 patients. A link was found between VUR and progressive MS course (p = 0.04), hydronephrosis (odds ratio [OR] = 17.44; 95% confidence interval [CI] = 3.46–87.87; p = 0.001), low GFR (p < 0.001), and detrusor overactivity (p = 0.04). No association with UTIs, EDSS, detrusor sphincter dyssynergia, were elicited. On multivariate analysis, alteration of GFR was independently related to the presence of VUR (OR = 0.95; 95% CI = 0.92–0.98).

Conclusions

VUR elicited on VCUG is associated with lower GFR and hydronephrosis. However, due to the low prevalence (5.5%) of this abnormality in PwMS, VCUG should be performed in selected cases and not in routinary practice.
INSIGHT responsive parenting educational intervention for firstborns is associated with growth of second‐born siblings
Authors: Savage Jennifer S. , Hochgraf Anna K. , Loken Eric , Marini Michele E. , Craig Sarah J. C. , Makova Kateryna D. , Birch Leann L. , Paul Ian M.
Published: December 2021

Objective

The aim of this study was to test whether the Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention, delivered to parents of firstborn children, is associated with the BMI of first‐ and second‐born siblings during infancy.

Methods

Participants included 117 firstborn infants enrolled in a randomized controlled trial and their second‐born siblings enrolled in an observation‐only ancillary study. The RP curriculum for firstborn children included guidance on feeding, sleep, interactive play, and emotion regulation. The control curriculum focused on safety. Anthropometrics were measured in both siblings at ages 3, 16, 28, and 52 weeks. Growth curve models for BMI by child age were fit.

Results

Second‐born children were delivered 2.5 (SD 0.9) years after firstborns. Firstborn and second‐born children whose parents received the RP intervention with their first child had BMI that was 0.44 kg/m2 (95% CI: −0.82 to 0.06) and 0.36 kg/m2 (95% CI: −0.75 to 0.03) lower than controls, respectively. Linear and quadratic growth rates for BMI for firstborn and second‐born cohorts were similar, but second‐born children had a greater average BMI at 1 year of age (difference = −0.33 [95% CI: −0.52 to −0.15]).

Conclusions

A RP educational intervention for obesity prevention delivered to parents of firstborns appears to spill over to second‐born siblings.
Interrelationships among age at adiposity rebound, BMI during childhood, and BMI after age 14 years in an electronic health record database
Authors: Freedman David S. , Goodwin‐Davies Amy J. , Kompaniyets Lyudmyla , Lange Samantha J. , Goodman Alyson B. , Phan Thao‐Ly Tam , Rao Suchitra , Eneli Ihuoma , Forrest Christopher B.
Published: December 2021

Objective

This study compared the importance of age at adiposity rebound versus childhood BMI to subsequent BMI levels in a longitudinal analysis.

Methods

From the electronic health records of 4.35 million children, a total of 12,228 children were selected who were examined at least once each year between ages 2 and 7 years and reexamined after age 14 years. The minimum number of examinations per child was six. Each child’s rebound age was estimated using locally weighted regression (lowess), a smoothing technique.

Results

Children who had a rebound age < 3 years were, on average, 7 kg/m2 heavier after age 14 years than were children with a rebound age ≥ 7 years. However, BMI after age 14 years was more strongly associated with BMI at the rebound than with rebound age (r = 0.57 vs. −0.44). Furthermore, a child’s BMI at age 3 years provided more information on BMI after age 14 years than did rebound age. In addition, rebound age provided no information on subsequent BMI if a child’s BMI at age 6 years was known.

Conclusions

Although rebound age is related to BMI after age 14 years, a child’s BMI at age 3 years provides more information and is easier to obtain.
Intervening on exercise and daylong movement for weight loss maintenance in older adults: A randomized, clinical trial
Authors: Fanning Jason , Rejeski W. Jack , Leng Iris , Barnett Cheyenne , Lovato James F. , Lyles Mary F. , Nicklas Barbara J.
Published: December 2021

Objective

This study aimed to determine the impact of dietary weight loss (WL) plus aerobic exercise (EX) and a “move more, more often” approach to activity promotion (SitLess; SL) on WL and maintenance.

Methods

Low‐active older adults (age 65‐86 years) with obesity were randomized to WL+EX, WL+SL, or WL+EX+SL. Participants received a social‐cognitive group‐mediated behavioral WL program for 6 months, followed by a 12‐month maintenance period. EX participants received guided walking exercise with the goal of walking 150 min/wk. SL attempted to achieve a step goal by moving frequently during the day. The primary outcome was body weight at 18 months, with secondary outcomes including weight regain from 6 to 18 months and objectively assessed physical activity and sedentary behavior at each time point.

Results

All groups demonstrated significant WL over 6 months (p < 0.001), with no group differences. Groups that received SL improved total activity time (p ≤ 0.05), and those who received EX improved moderate‐to‐vigorous activity time (p = 0.003). Over the 12‐month follow‐up period, those who received WL+EX demonstrated greater weight regain (5.2 kg; 95% CI: 3.5‐6.9) relative to WL+SL (2.4 kg; 95% CI: 0.8‐4.0).

Conclusions

Pairing dietary WL with a recommendation to accumulate physical activity contributed to similar WL and less weight regain compared with traditional aerobic exercise.
Coulomb branch global symmetry and quiver addition
Authors: Gledhill Kirsty , Hanany Amihay
Published: December 2021

Abstract

To date, the best effort made to simply determine the Coulomb branch global symmetry of a theory from a 3d$$ \mathcal{N} $$
N
= 4 quiver is by applying an algorithm based on its balanced gauge nodes. This often gives the full global symmetry, but there have been many cases seen where it instead gives only a subgroup. This paper presents a method for constructing several families of 3d$$ \mathcal{N} $$
N
= 4 unitary quivers where the true global symmetry is enhanced from that predicted by the balance algorithm, motivated by the study of Coulomb branch Hasse diagrams. This provides a rich list of examples on which to test improved algorithms for unfailingly identifying the Coulomb branch global symmetry from a quiver.
Small cosmological constants in string theory
Authors: Demirtas Mehmet , Kim Manki , McAllister Liam , Moritz Jakob , Rios-Tascon Andres
Published: December 2021

Abstract

We construct supersymmetric AdS4 vacua of type IIB string theory in compactifications on orientifolds of Calabi-Yau threefold hypersurfaces. We first find explicit orientifolds and quantized fluxes for which the superpotential takes the form proposed by Kachru, Kallosh, Linde, and Trivedi. Given very mild assumptions on the numerical values of the Pfaffians, these compactifications admit vacua in which all moduli are stabilized at weak string coupling. By computing high-degree Gopakumar-Vafa invariants we give strong evidence that the α′ expansion is likewise well-controlled. We find extremely small cosmological constants, with magnitude < 10−123 in Planck units. The compactifications are large, but not exponentially so, and hence these vacua manifest hierarchical scale-separation, with the AdS length exceeding the Kaluza-Klein length by a factor of a googol.
On warped string vacuum profiles and cosmologies. Part II. Non-supersymmetric strings
Authors: Mourad J. , Sagnotti A.
Published: December 2021

Abstract

We investigate the effects of the leading tadpole potentials of 10D tachyon-free non-supersymmetric strings in warped products of flat geometries of the typeMp+1× R × T10−p−2depending on a single coordinate. In the absence of fluxes and forp <8, there are two families of these vacua for the orientifold disk-level potential, both involving a finite internal interval. Their asymptotics are surprisingly captured by tadpole-free solutions, isotropic for one family and anisotropic at one end for the other. In contrast, for the heterotic torus-level potential there are four types of vacua. Their asymptotics are always tadpole-dependent and isotropic at one end lying at a finite distance, while at the other end, which can lie at a finite or infinite distance, they can be tadpole-dependent isotropic or tadpole-free anisotropic. We then elaborate on the general setup for including symmetric fluxes, and present the three families of exact solutions that emerge when the orientifold potential and a seven-form flux are both present. These solutions include a pair of boundaries, which are always separated by a finite distance. In the neighborhood of one, they all approach a common supersymmetric limit, while the asymptotics at the other boundary can be tadpole-free isotropic, tadpole-free anisotropic or again supersymmetric. We also discuss corresponding cosmologies, with emphasis on their climbing or descending behavior at the initial singularity. In some cases the toroidal dimensions can contract during the cosmological expansion.
Strategiewechsel zur minimal-invasiven Ösophagektomie – Ergebnisse an einem zertifizierten Zentrum
Authors: Merboth Felix , Hasanovic Jasmin , Stange Daniel , Distler Marius , Kaden Sandra , Weitz Jürgen , Welsch Thilo
Published: December 2021

Hintergrund

Es gibt Hinweise, dass die roboterassistierte minimal-invasive Ösophagektomie (RAMIE) die Morbidität im Vergleich zur konventionellen Operationstechnik verringern kann.

Ziel der Arbeit

Es erfolgte eine Vergleichsanalyse eines Single-Center-Strategiewechsels des Standards von offener Ösophagektomie zu RAMIE mit perioperativer, enteraler, selektiver Darmdekontamination (SDD).

Material und Methoden

Patienten- und Morbiditätsdaten nach elektiver RAMIE entsprechend dem neuen Standardmanagement zwischen Juli 2018 und September 2020 wurden retrospektiv mit einer historischen Kontrollkohorte nach offener Ösophagektomie zwischen Januar 2014 und Juni 2018 verglichen. Es erfolgte eine 1:1-Propensity-Score-Matching(PSM)-Analyse.

Ergebnisse

Insgesamt 75 Patienten konnten nach PSM in beiden Gruppen analysiert werden. Etwa zwei Drittel der Operationen erfolgte aufgrund eines Adenokarzinoms und ein Drittel bei Plattenepithelkarzinom. Im Median wurden 22 bzw. 21 Lymphknoten reseziert. Die intrathorakale Ösophagogastrostomie erfolgte in der RAMIE-Gruppe in 97 % mit einem Zirkularstapler mit ≥28 mm Durchmesser (offen: 25 mm in 90 % der Fälle). Die Operationszeit war länger (Median 490 vs. 339 min, p < 0,001), hingegen waren der Blutverlust (Median 300 vs. 500 ml, p < 0,001), die Anastomoseninsuffizienz- (8,0 % vs. 25,3 %, p = 0,004), Wundinfektions- (4,0 % vs. 17,3 %, p = 0,008) und pulmonale Komplikationsrate (29,3 % vs. 44,0 %, p = 0,045) sowie die mediane Krankenhausverweildauer (14 vs. 20 Tage, p < 0,001) und die 90-Tage-Mortalität signifikant geringer verglichen mit der offenen Kontrollkohorte (4,0 % vs. 13,3 %, p = 0,039).

Diskussion

Ein konsequenter Wechsel des perioperativen Managements u. a. mit RAMIE und SDD kann zu einer stabilen Reduktion der Morbidität ohne Einschränkungen der onkologischen Radikalität führen.
The mental health of young people who are not in education, employment, or training: a systematic review and meta-analysis
Authors: Gariépy Geneviève , Danna Sofia M. , Hawke Lisa , Henderson Joanna , Iyer Srividya N.
Published: December 2021

Purpose

There are increasing concerns about the intersection between NEET (not in education, employment, or training) status and youth mental ill-health and substance use. However, findings are inconsistent and differ across types of problems. This is the first systematic review and meta-analysis (PROSPERO-CRD42018087446) on the association between NEET status and youth mental health and substance use problems.

Methods

We searched Medline, EMBASE, Web of Science, ERIC, PsycINFO, and ProQuest Dissertations and Theses (1999–2020). Two reviewers extracted data and appraised study quality using a modified Newcastle–Ottawa Scale. We ran robust variance estimation random-effects models for associations between NEET and aggregate groups of mental ill-health and substance use measures; conventional random-effects models for associations with individual mental/substance use problems; and subgroup analyses to explore heterogeneity.

Results

We identified 24 studies from 6,120 references. NEET status was associated with aggregate groups of mental ill-health (OR 1.28, CI 1.06–1.54), substance use problems (OR 1.43, CI 1.08–1.89), and combined mental ill-health and substance use measures (OR 1.38, CI 1.15–1.64). Each disaggregated measure was associated with NEET status [mood (OR 1.43, CI 1.21–1.70), anxiety (OR 1.55, CI 1.07–2.24), behaviour problems (OR 1.49, CI 1.21–1.85), alcohol use (OR 1.28, CI 1.24–1.46), cannabis use (OR 1.62, CI 1.07–2.46), drug use (OR 1.99, CI 1.19–3.31), suicidality (OR 2.84, CI 2.04–3.95); and psychological distress (OR 1.10, CI 1.01–1.21)]. Longitudinal data indicated that aggregate measures of mental health problems and of mental health and substance use problems (combined) predicted being NEET later, while evidence for the inverse relationship was equivocal and sparse.

Conclusion

Our review provides evidence for meaningful, significant associations between youth mental health and substance use problems and being NEET. We, therefore, advocate for mental ill-health prevention and early intervention and integrating vocational supports in youth mental healthcare.
Combining the quantitative faecal immunochemical test and full blood count reliably rules out colorectal cancer in a symptomatic patient referral pathway
Authors: Johnstone Mark S. , Burton Paul , Kourounis Georgios , Winter Jack , Crighton Emilia , Mansouri David , Witherspoon Paul , Smith Karen , McSorley Stephen T.
Published: December 2021

Purpose

Faecal Immunochemical Test (FIT) has proven utility for Colorectal Cancer (CRC) detection in symptomatic patients. Most studies have examined FIT in symptomatic patients subsequently referred from primary care. We investigated associations between CRC and FIT in both referred and non-referred symptomatic patients.

Methods

A retrospective, observational study of all patients with a FIT submitted Aug 2018 to Jan 2019 in NHS GG&C was performed. Referral to colorectal/gastroenterology and decision to perform colonoscopy were recorded. FIT results were grouped as f-Hb < 10/10–149/150–399/ ≥ 400 μg/g. The MCN cancer registry identified new cases of CRC. Covariables were compared using theχ2 test. Multivariate binary logistic regression identified independent predictors of CRC.

Results

A total of 4968 patients were included. Raised FIT correlated with decision to refer (p < 0.001) and scope (p < 0.001). With 23-month median follow-up, 61 patients were diagnosed with CRC. These patients were older (median 69 vs 59 years, cancer and no cancer respectively,p = 0.001), more likely to be male (55.7% vs 42.1%,p = 0.033), and to report rectal bleeding (51.7% vs 36.1%,p = 0.013). FIT (< 10 µg/g 8.2% vs 76.7% and ≥ 400 µg/g 55.7% vs 3.8%,p < 0.001) and anaemia (45.9% vs 19.7%,p < 0.001) were associated with CRC. On multivariate analysis, age (p = 0.023), male sex (p = 0.04), FIT (≥ 400 OR 54.256 (95% CI:20.683–142.325;p < 0.001)), and anaemia (OR 1.956 (1.071–3.574;p = 0.029)) independently predicted CRC. One patient (0.04%) with a negative FIT and normal haemoglobin had CRC.

Conclusion

GP referral and secondary care investigation patterns were influenced by FIT. The combination of normal Hb and f-Hb excluded CRC in 99.96% of cases, providing excellent reassurance to those prioritising access to endoscopy services.
The Di models method: geological 3-D modeling of detrital systems consisting of varying grain fractions to predict the relative lithological variability for a multipurpose usability
Authors: Albarrán-Ordás Alberto , Zosseder Kai
Published: December 2021

The coexistence of a wide variety of subsurface uses in urban areas requires increasingly demanding geological prediction capacities for characterizing the geological heterogeneities at a small-scale. In particular, detrital systems are characterized by the presence of highly varying sediment mixtures which control the non-constant spatial distribution of properties, therefore presenting a crucial aspect for understanding the small-scale spatial variability of physical properties. The proposed methodology uses the lithological descriptions from drilled boreholes and implements sequential indicator simulation to simulate the cumulative frequencies of each lithological class in the whole sediment mixture. The resulting distributions are expressed by a set of voxel models, referred to asDimodels. This solution is able to predict the relative amounts of each grain fraction on a cell-by-cell basis and therefore also derive a virtual grain size distribution. Its implementation allows the modeler to flexibly choose both the grain fractions to be modeled and the precision in the relative quantification. The concept of information entropy is adapted as a measure of the disorder state of the clasts mixture, resulting in the concept of “Model Lithological Uniformity,” proposed as a measure of the degree of detrital homogeneity. Moreover, the “Most Uniform Lithological Model” is presented as a distribution of the most prevailing lithologies. This method was tested in the city of Munich (Germany) using a dataset of over 20,000 boreholes, providing a significant step forward in capturing the spatial heterogeneity of detrital systems and addressing model scenarios for applications requiring variable relative amounts of grain fractions.
Impacts of synergies on software project scheduling
Authors: Kosztyán Zsolt T. , Bogdány Eszter , Szalkai István , Kurbucz Marcell T.
Published: December 2021

The adequate allocation of human resources is one of the most important success factors in software projects. Although project teams can be regarded as complex systems in which a team’s performance is highly influenced by the interdependencies among team members, the allocation methods applied to date have focused only on individual skills and consider project teams as units of isolated workers. The existing software project scheduling problem (SPSP) is extended to (1) consider different skills and efficiencies of employees and (2) examine the pairwise synergies between them, as well as to (3) handle the flexible structure of the project that is used in flexible management, such as agile project management. To better understand the impact of synergies on the project’s cost, the solutions of the traditional and extended SPSP versions are analyzed and compared on the generated project networks. The results show not only that this factor has a highly significant impact but also that the project cost strongly depends on the structural parameters of the synergy network (e.g., topology, network size and degree centrality). Among these parameters, a low degree of centrality and some topologies, most notably star and circular networks, obtained the highest reduction in the projects’ total cost.
A Hurwitz divisor on the moduli of Prym curves
Authors: Bud Andrei
Published: December 2021

For even genus$$g=2i\ge 4$$g=2i≥4and the length$$g-1$$g-1partition$$\mu = (4,2,\ldots ,2,-2,\ldots ,-2)$$μ=(4,2,…,2,-2,…,-2)of 0, we compute the first coefficients of the class of$$\overline{D}(\mu )$$D¯(μ)in$$\mathrm {Pic}_{\mathbb {Q}}(\overline{{\mathcal {R}}}_g)$$PicQ(R¯g), where$$D(\mu )$$D(μ)is the divisor consisting of pairs$$[C,\eta ]\in {\mathcal {R}}_g$$[C,η]∈Rgwith$$\eta \cong {\mathcal {O}}_C(2x_1+x_2+\cdots + x_{i-1}-x_i-\cdots -x_{2i-1})$$η≅OC(2x1+x2+⋯+xi-1-xi-⋯-x2i-1)for some points$$x_1,\ldots , x_{2i-1}$$x1,…,x2i-1onC. We further provide several enumerative results that will be used for this computation.
Clustering Treatment Outcomes in Women with Gambling Disorder
Authors: Lara-Huallipe Milagros Lizbeth , Granero Roser , Fernández-Aranda Fernando , Gómez-Peña Mónica , Moragas Laura , del Pino-Gutierrez Amparo , Valenciano-Mendoza Eduardo , Mora-Maltas Bernat , Baenas Isabel , Etxandi Mikel , Menchón José M. , Jiménez-Murcia Susana
Published: December 2021

The rising prevalence of gambling disorder (GD) among women has awakened considerable interest in the study of therapeutic outcomes in females. This study aimed to explore profiles of women seeking treatment for GD based on a set of indicators including sociodemographic features, personality traits, clinical state at baseline, and cognitive behavioral therapy (CBT) outcomes. Two-step clustering, an agglomerative hierarchical classification system, was applied to a sample of n = 163 women of ages ranging from 20 to 73 years-old, consecutively attended to by a clinical unit specialized in the treatment of G. Three mutually exclusive clusters were identified. Cluster C1 (n = 67, 41.1%) included the highest proportion of married, occupationally active patients within the highest social status index. This cluster was characterized by medium GD severity levels, the best psychopathological functioning, and the highest mean in the self-directedness trait. C1 registered 0% dropouts and only 14.9% relapse. Cluster C2 (n = 63; 38.7%) was characterized by the lowest GD severity, medium scores for psychopathological measures and a high risk of dropout during CBT. Cluster C3 (n = 33; 20.2%) registered the highest GD severity, the worst psychopathological state, the lowest self-directedness level and the highest harm-avoidance level, as well as the highest risk of relapse. These results provide new evidence regarding the heterogeneity of women diagnosed with GD and treated with CBT, based on the profile at pre- and post-treatment. Person-centered treatments should include specific strategies aimed at increasing self-esteem, emotional regulation capacities and self-control of GD women.
Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting
Authors: Hudgens Stacie , Howerter Amy , Polek Ela , Andersson Fredrik L.
Published: December 2021

Purpose

Psychometric evaluation of the Nocturia Impact (NI) Diary was conducted to support its use as a trial endpoint.

Methods

As part of a randomized, controlled Phase 2 clinical trial investigating a novel drug candidate for nocturnal polyuria, adult nocturia patients completed the NI Diary and a voiding diary for three nights preceding their clinic visit at Baseline and Weeks 1, 4, 8, and 12 (end of treatment). Exit interviews were conducted to obtain patient impressions of the NI Diary.

Results

A total of N = 302 participants were included. Confirmatory factor analysis (CFA) indicated that the 11-item measure is unidimensional with values of CFI, TLI, and RMSEA meeting relevant thresholds. Good internal consistency (Cronbach’s α 0.941) and test–retest reliability (intra-class correlation coefficients 0.730–0.880). Convergent validity with two reference measures was demonstrated with strong correlations of 0.573–0.730 were shown. Significant differences (P = 0.0018, standardized effect size = 0.372) between groups defined by number of night-time voids supported known-groups validity. Exit interviews in 66 patients indicated all participants experienced improvement in at least 1 NI Diary item and that a 1-point improvement on the item response scale and 1-void reduction per night (associated with an average best cut point on ROC analysis of − 11.6) constituted meaningful improvement. Anchor and distribution-based analyses identified a meaningful change threshold of − 15 to − 18 points on the NI Diary.

Conclusion

The NI Diary is a reliable and valid patient-reported psychometric instrument which is fit-for-purpose to evaluate the impact of nocturia on patient quality of life in the clinical trial setting.

Trial registration number and registration date NCT03201419; June 28, 2017.
Wavelet-based robust estimation and variable selection in nonparametric additive models
Authors: Amato Umberto , Antoniadis Anestis , Feis Italia De , Gijbels Irène
Published: December 2021

This article studies M-type estimators for fitting robust additive models in the presence of anomalous data. The components in the additive model are allowed to have different degrees of smoothness. We introduce a new class of wavelet-based robustM-type estimators for performing simultaneous additive component estimation and variable selection in such inhomogeneous additive models. Each additive component is approximated by a truncated series expansion of wavelet bases, making it feasible to apply the method to nonequispaced data and sample sizes that are not necessarily a power of 2. Sparsity of the additive components together with sparsity of the wavelet coefficients within each component (group), results into a bi-level group variable selection problem. In this framework, we discuss robust estimation and variable selection. A two-stage computational algorithm, consisting of a fast accelerated proximal gradient algorithm of coordinate descend type, and thresholding, is proposed. When using nonconvex redescending loss functions, and appropriate nonconvex penalty functions at the group level, we establish optimal convergence rates of the estimates. We prove variable selection consistency under a weak compatibility condition for sparse additive models. The theoretical results are complemented with some simulations and real data analysis, as well as a comparison to other existing methods.
Product-form estimators: exploiting independence to scale up Monte Carlo
Authors: Kuntz Juan , Crucinio Francesca R. , Johansen Adam M.
Published: December 2021

We introduce a class of Monte Carlo estimators that aim to overcome the rapid growth of variance with dimension often observed for standard estimators by exploiting the target’s independence structure. We identify the most basic incarnations of these estimators with a class of generalized U-statistics and thus establish their unbiasedness, consistency, and asymptotic normality. Moreover, we show that they obtain the minimum possible variance amongst a broad class of estimators, and we investigate their computational cost and delineate the settings in which they are most efficient. We exemplify the merger of these estimators with other well known Monte Carlo estimators so as to better adapt the latter to the target’s independence structure and improve their performance. We do this via three simple mergers: one with importance sampling, another with importance sampling squared, and a final one with pseudo-marginal Metropolis–Hastings. In all cases, we show that the resulting estimators are well founded and achieve lower variances than their standard counterparts. Lastly, we illustrate the various variance reductions through several examples.
In vitro tools for orally inhaled drug products—state of the art for their application in pharmaceutical research and industry and regulatory challenges
Authors: Metz Julia Katharina , Hittinger Marius , Lehr Claus-Michael
Published: December 2021

The drug development process is a lengthy and expensive challenge for all involved players. Experience with the COVID-19 pandemic underlines the need for a rapid and effective approval for treatment options. As essential prerequisites for successful drug approval, a combination of high-quality studies and reliable research must be included. To this day, mainly in vivo data are requested and collected for assessing safety and efficacy and are therefore decisive for the pre-clinical evaluation of the respective drug. This review aims to summarize the current state of the art for safety and efficacy studies in pharmaceutical research and industry to address the relevant regulatory challenges and to provide an outlook on implementing more in vitro methods as alternative to animal testing. While the public demand for alternative methods is becoming louder, first examples have meanwhile found acceptance in relevant guidelines, e.g. the OECD guidelines for skin sensitizer. Besides ethically driven developments, also the rather low throughput and relatively high costs of animal experiments are forcing the industry towards the implementation of alternative methods. In this context, the development of orally inhaled drug products is particularly challenging due to the complexity of the lung as biological barrier and route of administration. The replacement of animal experiments with focus on the lungs requires special designed tools to achieve predictive data. New in vitro test systems of increasing complexity are presented in this review. Limits and advantages are discussed to provide some perspective for a future in vitro testing strategy for orally inhaled drug products.

Graphical abstract
Understanding National Remedies and the Principle of National Procedural Autonomy: A Constitutional Approach
Authors: HALBERSTAM Daniel
Published: December 2021

This article provides a constitutionally grounded understanding of the vexing principle of ‘national procedural autonomy’ that haunts the vindication of EU law in national court. After identifying tensions and confusion in the debate surrounding this purported principle of ‘autonomy’, the Article turns to the foundational text and structure of Union law to reconstruct the proper constitutional basis for deploying or supplanting national procedures and remedies. It further argues that much of the case law of the Court of Justice of the European Union may be considered through the lens of ‘prudential avoidance’, ie the decision to avoid difficult constitutional questions surrounding the principle of conferral. As the last Part shows, a constitutional understanding of ‘national procedural authority’—not ‘autonomy’—helps clear up some persistent puzzles, and provides critical guidance for when deference to national procedures and remedies is appropriate, and when such deference is misplaced. Comparative references inform the argument along the way.
Closing the rehabilitation utilization gap of New Zealand’s (Aotearoa) Māori people: Multiple case studies
Authors: Mpofu Ngonidzashe , Anderson Sasha , Brown Caroline , Yoo Minna
Published: December 2021

We aimed to explore personal factors in use of rehabilitation counseling and mental health services by Māori adults. Participants were three Māori adults (females = 2, residing in major urban settings, age range 45–50 years old; male = 1, residing in a rural setting, age range = 25–30 years old). Thematic analysis yielded the following findings: (a) a preference of Māori service providers who understand whānau culture, (b) an understanding of whakapapa or the family structure as an integral source of social support as counselors are planning for treatment, (c) establishing and maintaining trusting relationships within the Māori community by non-Māori counselors, (d) having financial difficulties when attempting to access rehabilitation resources, (e) limited access to health care facilities and services or lack of information about the services available, and (f) a general mistrust of government operated systems. Rehabilitation and mental health services with Māori should address personal cultural and systemic exclusion factors for better service engagement.
Methodological challenges in harmonisation of the variables used as indicators of social capital in epidemiological studies of ageing – results of the ATHLOS project
Authors: Zawisza Katarzyna , Woźniak Barbara , Tobiasz-Adamczyk Beata , Galas Aleksander , Giné-Vázquez Iago , Sanchez-Niubo Albert , Ayuso-Mateos José Luis , Koskinen Seppo , Leonardi Matilde , Bobak Martin , Haro Josep Maria
Published: December 2021

The present article aims to highlight methodological aspects related to understanding and conceptualising social capital for the purposes of population research as well as describing the key challenges in the harmonisation process of indicators of social capital. The study was conducted in the frame of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project. After a review of social capital theories developed in social science and a subsequent review of the documentation of 18 international cohorts, decision trees of the harmonisation of social variables were developed. The known-group validity was verified. The results focused on generalised trust, civic engagement and social participation are presented. The summary of the availability of any indicators of these concepts is classified in seven domains (generalised trust, political participation, religious participation, senior-specific participation, participation in sport groups, participation in volunteer/charity group activities, any participation) across surveys. The results of the analysis for known-group validity support the construct validity of the harmonised variables.
The Lie of the Land: Decadence, Ecology, and Arboreal Communications
Authors: Denisoff Dennis
Published: December 2021

Focusing on Vernon Lee's and Algernon Blackwood's portrayals of forests, this article argues that decadent ecology questions the privileging of humans over other sentient beings in relation to the moral conscriptions intending to channel attachments and desires toward productivist purposes. It addresses the ways in which these authors undermine human assumptions of self-control and managerial authority by encouraging an opening up to the affective communications of ecosystems. Raising questions central to eco-studies in general, Lee's and Blackwood's works challenge ideas of human communicative superiority and extensionism through representations of humility, trepidatious veneration, and a sense of the imagination as a potential channel for affection across species.
Verdeurs: Oscar Wilde, Dorian Gray, and the Colors of Decadence
Authors: Ribeyrol Charlotte
Published: December 2021

When Basil Hallward discovers the distorted portrait of Dorian Gray in chapter 13 of Wilde's eponymous novel, he first ascribes the changes to “some wretched mineral poison” in his paints. Although the passage corresponds to the climax of the story, it has rarely been discussed from a chromatic perspective. And yet, color mattered to Wilde as well as to many of his decadent friends. Drawing on the canonical text of The Picture of Dorian Gray (1891), which it revisits from a color perspective, this article explores the literary inscription of new, shifting chromatic materialities in order to shed light on what Théophile Gautier, in his seminal 1868 essay on Baudelaire, defined as the decadent “palette”: “veined with the greenness (verdeurs) of decomposition.”
Mesoscale Eddies Regulate Seasonal Iron Supply and Carbon Drawdown in the Drake Passage
Authors: Jersild Annika , Delawalla Sara , Ito Takamitsu
Published: December 2021

The Southern Ocean is a major region for uptake of anthropogenic carbon. The transport of carbon and nutrients are dominated by the Antarctic Circumpolar Current and its rich mesoscale eddy field; however, the current generation of Earth System Models (ESMs) lack the resolution to resolve eddies. Here we show that a computational model that explicitly represents mesoscale eddies can reproduce observed phases and amplitudes of seasonal biological productivity and partial pressure of carbon dioxide. Our sensitivity study demonstrates that when eddies are suppressed or parameterized, the model cannot reproduce these seasonal cycles. Experiments with suppressed eddy activity show that the lack of eddies significantly changes the iron supply and phenology of phytoplankton blooms. The mismatch in the timing and intensity of the bloom causes significant biases in the seasonal carbon cycle of the region with implications to the enigmatic biases in partial pressure of carbon dioxide among the state‐of‐the‐art ESMs.
Sub‐Kilometer Correlation Between Near‐Surface Structure and Ground Motion Measured With Distributed Acoustic Sensing
Authors: Yang Yan , Atterholt James W. , Shen Zhichao , Muir Jack B. , Williams Ethan F. , Zhan Zhongwen
Published: December 2021

Earthquake ground motion depends strongly on near‐surface structure, which is challenging to image in urban areas at high resolution. Distributed acoustic sensing (DAS) is an emerging technique that provides a scalable solution by converting preexisting fiber‐optic cables into dense seismic arrays. After the July 2019 M7.1 Ridgecrest earthquake, we converted an underground dark fiber across the city of Ridgecrest, CA, into a DAS array. The recorded aftershocks show substantial lateral variability in site amplification over only 8‐km in distance. To understand the cause of such variability, we used three months of continuous data, dominated by traffic‐generated seismic noise, to image near‐surface structure along the fiber path. We find that the lateral variations of earthquake shaking correlate well with the shallow shear velocity model at sub‐kilometer scales, in particular micro‐basins filled with soft sediments. These results highlight the great potential of DAS for high‐resolution seismic hazard mapping in urban areas.
Deep Sourced Fluids for Peridotite Carbonation in the Shallow Mantle Wedge of a Fossil Subduction Zone: Sr and C Isotope Profiles of OmanDP Hole BT1B
Authors: de Obeso Juan Carlos , Kelemen Peter B. , Leong James M. , Menzel Manuel D. , Manning Craig E. , Godard Marguerite , Cai Yue , Bolge Louise ,   Oman Drilling Project Phase 1 Science Party
Published: December 2021

Completely carbonated peridotites represent a window to study reactions of carbon‐rich fluids with mantle rocks. Here, we present details on the carbonation history of listvenites close to the basal thrust in the Samail ophiolite. We use samples from Oman Drilling Project Hole BT1B, which provides a continuous record of lithologic transitions, as well as outcrop samples from listvenites, metasediments, and metamafics below the basal thrust of the ophiolite. 87Sr/86Sr of listvenites and serpentinites, ranging from 0.7090 to 0.7145, are significantly more radiogenic than mantle values, Cretaceous seawater, and other peridotite hosted carbonates in Oman. The Hawasina sediments that underlie the ophiolite, on the other hand, show higher 87Sr/86Sr values of up to 0.7241. δ13C values of total carbon in the listvenites and serpentinites range from −10.6‰ to 1.92‰. We also identified a small organic carbon component with δ13C as low as −27‰. Based on these results, we propose that during subduction at temperatures above >400°C, carbon‐rich fluids derived from decarbonation of the underlying sediments migrated updip and generated the radiogenic 87Sr/86Sr signature and the fractionated δ13C values of the serpentinites and listvenites in core BT1B.
Organic Matter Composition of Biomineral Flocs and Its Influence on Suspended Particulate Matter Dynamics Along a Nearshore to Offshore Transect
Authors: Fettweis Michael , Schartau Markus , Desmit Xavier , Lee Byung Joon , Terseleer Nathan , Van der Zande Dimitry , Parmentier Koen , Riethmüller Rolf
Published: December 2021

The seasonal variation in concentration of transparent exopolymer particles (TEPs), particulate organic carbon (POC) and particulate organic nitrogen (PON) were investigated together with floc size and the concentration of suspended particulate matter (SPM) along the cross‐shore gradient, from the high turbid nearshore toward the low‐turbid offshore waters in the Southern Bight of the North Sea. Our data demonstrate that biophysical flocculation cannot be explained by these heterogeneous parameters, but requires a distinction between a more reactive labile (“fresh”) and a less reactive refractory (“mineral‐associated”) fraction. Based on all data, we separated the labile and mineral‐associated POC, PON, and TEP using a semi‐empirical model approach. The model's estimates of fresh and mineral‐associated organic matter (OM) show that great parts of the POC, PON, and TEP are associated with suspended minerals, which are present in the water column throughout the year, whereas the occurrence of fresh TEP, POC, and PON is restricted to spring and summer months. In spite of a constantly high abundance of total TEP throughout the entire year, it is its fresh fraction that promotes the formation of larger and faster sinking biomineral flocs, thereby contributing to reducing the SPM concentration in the water column over spring and summer. Our results show that the different components of the SPM, such as minerals, extracellular OM and living organisms, form an integrated dynamic system with direct interactions and feedback controls.
Efficient technique of microarray missing data imputation using clustering and weighted nearest neighbour
Authors: Dubey Aditya , Rasool Akhtar
Published: December 2021

For most bioinformatics statistical methods, particularly for gene expression data classification, prognosis, and prediction, a complete dataset is required. The gene sample value can be missing due to hardware failure, software failure, or manual mistakes. The missing data in gene expression research dramatically affects the analysis of the collected data. Consequently, this has become a critical problem that requires an efficient imputation algorithm to resolve the issue. This paper proposed a technique considering the local similarity structure that predicts the missing data using clustering and top K nearest neighbor approaches for imputing the missing value. A similarity-based spectral clustering approach is used that is combined with the K-means. The spectral clustering parameters, cluster size, and weighting factors are optimized, and after that, missing values are predicted. For imputing each cluster’s missing value, the top K nearest neighbor approach utilizes the concept of weighted distance. The evaluation is carried out on numerous datasets from a variety of biological areas, with experimentally inserted missing values varying from 5 to 25%. Experimental results prove that the proposed imputation technique makes accurate predictions as compared to other imputation procedures. In this paper, for performing the imputation experiments, microarray gene expression datasets consisting of information of different cancers and tumors are considered. The main contribution of this research states that local similarity-based techniques can be used for imputation even when the dataset has varying dimensionality and characteristics.
The transfer and persistence of metals in latent fingermarks
Authors: Boseley Rhiannon E. , Howard Daryl L. , Hackett Mark J. , Lewis Simon W.
Published: December 2021

Transfer and persistence of metals in latent fingermarks derived from objects of forensic interest explored using synchrotron sourced X-ray fluorescence microscopy.
High sensitivity and rapid detection of hepatitis B virus DNA using lateral flow biosensors based on Au@Pt nanorods in the absence of hydrogen peroxide
Authors: Li Niu , Xi Xiaoxue , Zhu Junlun , Wu Xiaowei , Zhang Xiuhua , Wang Shengfu , Wen Wei
Published: December 2021

Au@Pt nanorods with enhanced oxidase-like activity were designed and used as signal probes to construct LFBs for the high sensitivity detection of hepatitis B virus DNA (HBV-DNA).
Electrocatalytic H2 evolution promoted by a bioinspired (N2S2)Ni(ii) complex
Authors: Sinha Soumalya , Tran Giang N. , Na Hanah , Mirica Liviu M.
Published: December 2021

We report a bioinspired (N2S2)Ni(ii) complex that catalyzes the electrochemical H2 evolution reaction (HER) with a turnover frequency (TOF) of ∼1250 s−1 at low acid concentration in acetonitrile.
P-Doped graphene–C60 nanocomposite: a donor–acceptor complex with a P–C dative bond
Authors: Lo Rabindranath , Manna Debashree , Hobza Pavel
Published: December 2021

Phosphorous-doped graphene can form a covalent dative bond with the electron acceptor, C60 molecule.
Tumour enzyme affinity mediated peptide molecular crowding for targeted disruption of hyperactivated glucose uptake
Authors: Kwek Germain , Lingesh Shonya , Chowdhury Sayba Zafrin , Xing Bengang
Published: December 2021

An unconventional environment-responsive molecular crowding via specific binding between small molecule peptide inhibitor derivatives and overexpressed tumour enzyme has been developed.
Plasmon-coupled Au-nanochain functionalized PEDOT:PSS for efficient mixed tin–lead iodide perovskite solar cells
Authors: Song Jiaxing , Yin Xinxing , Hu Lin , Su Zhen , Jin Yingzhi , Deng Dan , Li Zaifang , Wang Guannan , Bao Qinye , Tian Wenjing
Published: December 2021

Au nanochains with a coupled plasmonic nanostructure were first introduced into PEDOT:PSS used as a HTL to fabricate mixed Sn–Pb PSCs.
Photo-Fries-type rearrangement of cyclic enamides. An efficient route to structurally diverse five-membered enaminones
Authors: Szcześniak Piotr , Furman Bartłomiej
Published: December 2021

An efficient approach for the synthesis of structurally diverse five-membered enaminones via a photo-Fries-type rearrangement of cyclic enamides in excellent yields is reported.
CO, CO2 and CS2 activation by divalent ytterbium hydrido complexes
Authors: Shi Xianghui , Rajeshkumar Thayalan , Maron Laurent , Cheng Jianhua
Published: December 2021

Treatment of a divalent ytterbium hydride complex 1 with CO, CO2 and CS2 resulted in the formation of a divalent ytterbium ethenediolate complex 2, a formate complex 3, and a trivalent ytterbium ethenetetrathiolate complex 4, respectively.
A multi-responsive luminescent sensor based on a stable Eu(iii) metal–organic framework for sensing Fe3+, MnO4−, and Cr2O72−in aqueous solutions
Authors: He Qi-Qi , Yao Shu-Li , Zheng Teng-Fei , Xu Hui , Liu Sui-Jun , Chen Jing-Lin , Li Na , Wen He-Rui
Published: December 2021

A stable benzothiadiazole-based Eu(iii) metal–organic framework withccotopology has been successfully constructed, and represents the multifunctional fluorescence sensor toward Fe3+, MnO4−and Cr2O72−in aqueous solutions.
Spontaneous desorption of protein from self-assembled monolayer (SAM)-coated gold nanoparticles induced by high temperature
Authors: Wang Shuai , Ou Xinwen , Yi Ming , Li Jingyuan
Published: December 2021

A more comprehensive understanding of nonspecific binding of protein with nanomaterial from the perspective of thermally induced spontaneous desorption.
Activation of CO2 and CH4 on MgO surfaces: mechanistic insights from first-principles theory
Authors: Manae Meghna A. , Dheer Lakshay , Rai Sandhya , Shetty Sharan , Waghmare Umesh V.
Published: December 2021

Using DFT calculations, we propose O-terminated (111) surface of MgO as a suitable catalyst for Oxidative Coupling of Methane as it cleaves 3 C—H bonds in CH4, and interacts weakly with CO2, a byproduct, thus avoiding poisoning via MgCO3 formation.
Structural order of water molecules around polyrotaxane including PEG, α-cyclodextrin, and α-lipoic acid linker on gold surface by molecular dynamics simulations
Authors: Le Tue Minh Nhu , Van Sang Le , Washizu Hitoshi
Published: December 2021

Water structure in polyrotaxane was classified through tetrahedral order and temperature by the molecular dynamics simulation method.
The degradation effect on proton dissociation and transfer in perfluorosulfonic acid membranes
Authors: Hu Yu , Wang Shuai , Gao Guohui , He Yurong
Published: December 2021

In the operation of proton exchange membrane fuel cells (PEMFCs), the ionomer-perfluorosulfonic acid (PSFA) membrane side chains are easily attacked by free radicals, resulting in membrane degradation.