bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trends in the epidemiology, management, and outcome of sepsis—A nationwide observational study
Authors: Vesteinsdottir Edda , Sigurdsson Martin Ingi , Gottfredsson Magnus , Blondal Asbjorn , Karason Sigurbergur
Published: January 2022

Background

Registry‐based studies have shown increasing incidence of sepsis and declining mortality rates in recent years, but are inherently at risk of bias. The objectives of this study were to describe 11‐year trends in the incidence, treatment and outcome of sepsis using clinical criteria with chart review.

Methods

This was a retrospective, observational study. All adult admissions to Icelandic ICUs during years 2006, 2008, 2010, 2012, 2014, and 2016 were screened for severe sepsis or septic shock by ACCP/SCCM criteria (sepsis‐2). Incidence, patient characteristics, treatment and outcome were compared across the study years.

Results

During the six study years, 9166 patients were admitted to Icelandic ICUs, 971 (10.6%) because of severe sepsis or septic shock. The crude incidence of sepsis requiring admission to ICU remained stable between 0.55 and 0.75 per 1000 inhabitants. No statistically significant trends were observed over time in median patient age (67 years), APACHE II score (21), SOFA score (8) or Charlson Comorbidity Index (4). The time to antibiotic administration (median 1.8 h) in the emergency departments was stable over the study period but the time to lactate measurements decreased from 4.1 h in 2006 to 1.2 h in 2016, p < .001. The 28‐day mortality was 25% and 1‐year mortality 41%, both with no observed change with time.

Conclusions

In a nationwide cohort, diagnosed with clinical criteria, the incidence of sepsis requiring intensive care did not change over an 11‐year period. Mortality remained stable and only minimal changes were observed in initial resuscitation in the emergency departments.
Phase 2, randomized multi oral immunotherapy with omalizumab ‘real life’ study
Authors: Sindher Sayantani B. , Kumar Divya , Cao Shu , Purington Natasha , Long Andrew , Sampath Vanitha , Zedeck Stacey S. , Woch Margaret A. , Garcia‐Lloret Maria , Chinthrajah Rebecca Sharon
Published: January 2022

Background

Oral immunotherapy (OIT) is frequently discontinued due to adverse events (AEs) and current data suggests that lowering OIT doses can minimize severity and frequency of AEs. However, the minimum daily dose that can enable desensitization and induce immune responses in multi‐food OIT (mOIT) is unknown.

Methods

Participants aged 2–25 years with multi‐food allergies were pretreated with fixed‐dose omalizumab (150 mg, 3 doses, every 4 weeks), and randomized 1:1 to receive mOIT to a total maintenance dose of either 300 or 1200 mg total protein, (total dose includes at least two and up to a max of five allergens) and then transitioned to real‐food protein equivalents after 18 weeks of treatment. The primary endpoint was the proportion of subjects with increases in IgG4/IgE ratio of at least 2 allergens by ≥25% from baseline after 18 weeks of therapy. The primary efficacy and safety analyses were done in the intention‐to‐treat population.

Results

Sixty participants were enrolled across two sites. Seventy percent of participants in both arms showed changes in sIgG4/sIgE ratio in at least 2 allergens with no difference between the treatment groups (OR [95% CI] = 1.00 [0.29, 3.49]). Overall, there were no differences in AEs between the 300 and 1200 mg groups (19% vs. 17%, p = .69), respectively.

Conclusions

Our data suggest that plasma marker changes are induced early, even at a total protein dose of 300 mg inclusive of multiple allergens when mOIT is combined with fixed‐dose omalizumab. Identification of optimal mOIT dosing with adjunct omalizumab is needed for the long‐term success of OIT.

Trial Registration

ClinicalTrials.gov (NCT03181009).
Long term efficacy of Video‐Assisted Anal Fistula Treatment (VAAFT) for complex fistula‐in‐ano: a single‐centre Australian experience
Authors: Hinksman Mat , Naidu Sanjeev , Loon Kenneth , Grundy Joshua
Published: January 2022

Background

Video‐Assisted Anal Fistula Treatment (VAAFT) is a novel minimally invasive & sphincter‐saving technique for treating complex fistula‐in‐ano involving endoscopic assessment & treatment of perianal fistula. This retrospective, non‐randomized, observational study is the first Australian study of VAAFT. It is also the longest study of VAAFT to‐date.

Methods

From January 2014 to September 2019, 59 patients with a complex anal fistula were identified via MRI & underwent VAAFT. Fourteen patients had undergone previous definitive surgery for anal fistula. Specialized Karl Storz video equipment (fistuloscope) was used in the procedure. The rigid fistuloscope was used to directly visualize the fistula tract/s & internal opening. Closure of the internal opening was then performed. The fistula tract/s were then treated via fulguration. The external opening was kept patent & dressed. Patients were then followed up for a mean 59.5 months.

Results

67.9% (n = 38) of patients achieved primary healing (needing nil further intervention) at a median of 13 weeks. 12.5% (n = 7) experienced healing followed by recurrence while 19.6% (n = 11) experienced non‐healing. Of the recurrence/non‐healing groups, 11/18 underwent repeat VAAFT with healing occurring in 10/11 patients at a median of 7 weeks. The mean operating time was 41.1 min. There were no major complications & continence scores were not affected. Three patients were lost to follow up.

Conclusion

VAAFT is both effective & safe for the treatment of complex fistula‐in‐ano. Its minimally invasive nature means that in the instance of recurrence or persistence, VAAFT can be repeated with minimal morbidity & reasonable likelihood of success.
Mobilising Rents: Natural Gas Production Networks and the Landlord State in Peru and Bolivia
Authors: Irarrázaval Felipe
Published: January 2022

The ongoing choreography of extractive industries asks for a deeper appraisal about the processes and scales underpinning resource extraction. This paper unpacks how the assembly between natural gas production networks, extractivist states and local politics is anchored in resource peripheries in Peru and Bolivia through contingent schemes of value distribution. From a critical production network approach, the paper examines the transformation of resource peripheries through the transfer of natural gas rents to sub‐national governments and, more specifically, through investments in public infrastructure. Such investments embed natural gas production networks to local politics through three processes: providing an image of modernisation and progress; coopting local elites through corruption; and mobilising local labour. In conclusion, the articulation between production networks and extractivist states involves an entangled scheme of rent distribution that flows at very local levels and consolidates multi‐scalar arrangements for resource extraction.
Urban Redevelopment, Displacement, and Governmentality in Nanjing’s Historic Inner‐City
Authors: Zhang Zhao , Moore‐Cherry Niamh
Published: January 2022

Housing‐related urban development has become a core plank of China’s economic policy since the mid‐1990s. Reports of resistance to displacement and resettlement associated with urban restructuring, once widespread, have dissipated since the early‐2010s. Using the framework of governmentality and through qualitative empirical fieldwork in the historic inner‐city of Nanjing, we try to understand the dynamics of this change. This research draws attention to how governments deploy new technologies and rationalities to regroup and push forward urban transformation. We highlight how more “advanced” disciplinary apparatuses both encourage neoliberal subjectivities among displacees and use authoritarian features to maintain the “order of things” in line with the desires of the Chinese state.
Pharmacokinetic characterization of favipiravir in patients with COVID‐19
Authors: Gülhan Rezzan , Eryüksel Emel , Gülçebi İdriz Oğlu Medine , Çulpan Yekta , Toplu Aylin , Kocakaya Derya , Tigen Elif , Ertürk Şengel Buket , Sili Uluhan , Olgun Yıldızeli Şehnaz , Balcan Mehmet Baran , Elçi Abdullah , Bulut Cenk , Karaalp Atila , Yananlı Hasan Raci , Güner Abdullah Emre , Hatipoğlu Mustafa , Karakurt Sait , Korten Volkan , Ratnaraj Neville , Patsalos Philip , Ay Pınar , Onat Filiz
Published: January 2022

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID‐19 with a positive RT‐PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in‐hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID‐19. The median favipiravir trough concentration (C0‐trough) on Day 2 was 21.26 (interquartile range [IQR], 8.37–30.78) μg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00–6.41) μg/mL on Day 4, the area under the concentration–time curve decreased by 68.5%. Day 2 C0‐trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID‐19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations.
Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple‐dose study
Authors: Kubitza Dagmar , Heckmann Michael , Distler Jana , Koechel Annemone , Schwers Stephan , Kanefendt Friederike
Published: January 2022

Aim

To evaluate BAY 2433334, an oral activated factor XI (FXIa) inhibitor, in volunteers.

Methods

Phase 1 study of healthy men at a German centre. Part A: randomized, single‐blind, multiple dose‐escalation study of BAY 2433334 (25/50/100 mg once daily [OD]) vs. placebo. Part B: similar design to Part A; evaluated BAY 2433334 25 mg twice daily. Part C: nonrandomized, open‐label study; evaluated potential interactions between BAY 2433334 (25/75 mg OD) and midazolam (7.5 mg), a CYP3A4 index substrate. Primary variables: treatment‐emergent adverse events (TEAEs; Parts A and B); area under the plasma concentration–time curve (AUC) and maximum plasma concentration of midazolam and α‐hydroxymidazolam (Part C). Study period: 18 days plus follow‐up visit.

Results

Parts A and B: 36 participants randomized to BAY 2433334; 12 to placebo. Part C: 48 participants assigned to BAY 2433334 plus midazolam. BAY 2433334 was well tolerated in all study parts. AUC and maximum plasma concentration of BAY 2433334 in plasma appeared dose proportional over 25–100 mg OD, with low‐to‐moderate variability in pharmacokinetic parameters. Multiple dosing caused minor‐to‐moderate accumulation and a mean terminal half‐life (15.8–17.8 h) supporting once‐daily dosing. Dose‐dependent FXIa activity inhibition and activated partial thromboplastin time prolongation were observed. BAY 2433334 appeared to have a minor effect on AUC for midazolam (ratio [90% confidence interval]: 1.1736 [1.0963–1.2564]) and α‐hydroxymidazolam (0.9864 [0.9169–1.0612]) only for BAY 2433334 75 mg OD on day 10.

Conclusion

Multiple dosing of BAY 2433334 in healthy volunteers was well tolerated, with a predictable pharmacokinetic/pharmacodynamic profile and no clinically relevant CYP3A4 induction or inhibition.
Efficacy of fibroblast growth factor 21 in non‐alcoholic fatty liver disease in guinea pigs
Authors: Klaebel Julie Hviid , Lykkesfeldt Jens , Tveden‐Nyborg Pernille
Published: January 2022

Fibroblast growth factor 21 (FGF21) agonists have shown promising effects in preclinical models of non‐alcoholic fatty liver disease (NAFLD) as well as in short‐term clinical trials in patients with non‐alcoholic steatohepatitis (NASH). Comparing drug formulation, dose, administration route and age, this exploratory study investigated effects of FGF21 on NAFLD‐associated measures in a validated guinea pig model. In three separate studies, female guinea pigs received a high‐fat diet prior to intervention with escalating doses of either recombinant native human FGF21 or a human FGF21 human recombinant analogue (FGF21/19 chimer) with an extended half‐life. While no significant effects of native FGF21 on the investigated endpoints were observed, the long‐acting FGF21/19 chimer significantly altered the levels of circulating lipids, increasing plasma concentrations of cholesterol (TC, LDLc and HDLc) in young guinea pigs (p < 0.01 for all three parameters). Relative liver weights were reduced in FGF21/19‐treated young animals (p < 0.05) compared to mature animals, whereas FGF21/19 reduced body weights in both age groups (p < 0.001). The FGF21/19 chimer effects on dyslipidemia, body and liver weights particularly in young animals, support an age‐associated difference in the FGF21 response. The limited effects of the native human FGF21 highlights potential species‐associated differences of this compound.
Forefront studies on human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis
Authors: Takao Naoki , Yamano Yoshihisa
Published: January 2022

Human T‐cell leukemia virus type 1 can cause human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T‐cell leukemia/lymphoma in some infected individuals. HAM/TSP is a rare progressive neurological disease characterized by spastic spinal paralysis. The developments in previous research have identified many aspects of the disease pathology. However, the disease is rarely cured, and the aims of treatment remain controlling long‐term progression. This study intends to describe the pathophysiology and treatments for HAM/TSP elucidated from recent studies and the HAM/TSP patient registry.
Genogeographic clustering to identify cross‐species concordance of spatial genetic patterns
Authors: Arranz Vanessa , Fewster Rachel M. , Lavery Shane D.
Published: January 2022

Aim

While in recent years, there have been considerable advances in discerning spatial genetic patterns within species, the task of identifying common patterns across species is still challenging. Approaches using new data from co‐sampled species permit rigorous statistical analysis but are often limited to a small number of species. Meta‐analyses of published data can encompass a much broader range of species, but are usually restricted by uneven data properties. There is a need for new approaches that bring greater statistical rigour to meta‐analyses and are also able to discern more than a single spatial pattern among species. We propose a new approach for comparative multi‐species meta‐analyses of published population genetic data that address many existing limitations.

Innovation

The proposed “genogeographic clustering” technique takes a three‐stage approach: (i) use common genetic metrics to gain location‐specific measures across the sampled range of each species; (ii) for each species, determine the spatial genetic pattern by fitting a smooth “genogeographic” trend curve to the genetic data; and (iii) quantitatively cluster species according to their similarity in spatial pattern. We apply this technique to 21 species of intertidal invertebrates from the New Zealand coastline, to resolve common spatial patterns from disparate profiles of genetic diversity.

Main conclusions

The genogeographic curves are shown to successfully capture the known spatial patterns within each intertidal species and readily permit statistical comparison of those patterns, regardless of sampling and marker inconsistencies. The species clustering technique is shown to discern groups of species that clearly share spatial patterns within groups but differ significantly among groups. Genogeographic species clustering provides a novel approach to discerning multiple common spatial patterns of diversity among a large number of species. It will permit more rigorous comparative studies from diverse published data and can be easily extended to a wide variety of alternative measures of genetic diversity or divergence.
Neural processing of moral content reflects moral identity in 10‐year‐old children
Authors: Pletti Carolina , Decety Jean , Paulus Markus
Published: January 2022

Middle childhood seems to be crucial for the emergence of a moral identity, that is, an evaluative stance of how important it is for someone's sense of self to be moral. This study investigates the effects of moral identity on the neural processing of moral content in 10‐year‐old children. Participants were presented with scenes portraying prosocial and antisocial behavior, while electroencephalographic responses were collected. Analyses of event‐related potentials (ERPs) showed that, for children with a strong moral identity, antisocial scenes elicited a greater early posterior negativity (EPN) as compared to prosocial scenes. Thus, for children with a strong moral identity, antisocial scenes capture more attentional resources than prosocial ones in early processing stages. In contrast to previous findings with adults, the implicit moral self‐concept was not related to any ERP differences. Overall, the results show that, even in its developmental emergence, moral identity relates to the neurocognitive processing of third‐party moral content. Together, the study supports the social‐cognitive model of the development of moral identity, according to which moral identity is based on a chronical activation of moral schemas that guide a person's perception of the social world.
Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID‐19 patients with diabetes: A population‐based study in Lombardy
Authors: Ojeda‐Fernández Luisa , Foresta Andreana , Macaluso Giulia , Colacioppo Pierluca , Tettamanti Mauro , Zambon Antonella , Genovese Stefano , Fortino Ida , Leoni Olivia , Roncaglioni Maria Carla , Baviera Marta
Published: January 2022

Aim

To compare the association of metformin use and coronavirus disease 2019 (COVID‐19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy.

Methods

We used a COVID‐19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus‐2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all‐cause mortality, in‐hospital mortality, hospitalization for COVID‐19, and admission to an intensive care unit (ICU).

Results

In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66‐0.75), in‐hospital mortality (OR 0.68; 95% CI 0.63‐0.73), hospitalization for COVID‐19 (OR 0.86; 95% CI 0.81‐0.91), and ICU admission (OR 0.81; 95% CI 0.69‐0.94) compared with metformin non‐users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73‐0.86), in‐hospital mortality (OR 0.74; 95% CI 0.67‐0.81), and ICU admission (OR 0.77; 95% CI 0.63‐0.95).

Conclusions

In this large cohort, metformin use was associated with a protective effect in COVID‐19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID‐19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID‐19 patients with diabetes.
Cleft posterior mitral valve leaflet: The added value of 3‐dimensional echocardiography
Authors: Rizk Judy , Abdel‐Hay Mohamed Ayman
Published: January 2022

A 65‐year‐old female patient diagnosed with degenerative aortic valve disease and severe regurgitation on transthoracic echocardiography (TTE) also had severe mitral regurgitation (MR), but the exact mechanism of MR could not be determined. Transesophageal echocardiography (TEE) showed limited leaflet coaptation and a severe central MR jet. Further three‐dimensional (3D) imaging revealed an indentation in the middle of P2 scallop almost reaching the annulus. This was consistent with the diagnosis of cleft posterior mitral valve leaflet. Unlike cleft anterior leaflet which can be clear on TTE short‐axis images, cleft posterior leaflet may only be visible using 3D TEE. The identification of cleft posterior leaflet is essential in guiding surgical valve repair.
The partisan divide in U.S. congressional communications after the China shock
Authors: Kuk John , Seligsohn Deborah , Zhang Jiakun Jack
Published: January 2022

Emerging literature shows that rising import exposure resulting from the China shock devastated U.S. manufacturing and contributed to the rise of Donald Trump. However, several studies found that these recent localized economic shocks did not negatively impact the tenure of incumbent politicians, and this outcome remains a puzzle. In this paper, we examine the partisan difference in congressional communication strategies on China and trade‐related issues. We propose a theory of China‐bashing to explain how members of Congress frame the negative impacts of trade to their voters. Using press release data from members of Congress, we show that, even though Chinese import competition impacted both Republican‐ and Democrat‐held districts, Republican politicians in adversely affected districts responded by increasing their anti‐China rhetoric, while there was no similar difference among Democrats. At the same time, there was no difference between Republican and Democratic messaging on general trade issues. In doing so, Republican legislators were able to support trade liberalization during the Bush and Obama administrations while blaming its negative externalities to their constituents on China.
Pregnancy‐induced brain magnetic resonance imaging changes in women with multiple sclerosis
Authors: Uher Tomas , Kubala Havrdova Eva , Vodehnalova Karolina , Krasensky Jan , Capek Vaclav , Vaneckova Manuela , Horakova Dana
Published: January 2022

Background and purpose

The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods.

Methods

This observational study of 62 women with relapsing–remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow‐up (>12 and <24 months after delivery) periods.

Results

The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow‐up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (‐1.74% vs. ‐0.16%) compared with the prepregnancy period (all p < 0.001). At 12–24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001).

Conclusions

The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision‐making and designing clinical trials.
Corneal neoplasia in horses
Authors: Malalana F.
Published: January 2022

Primary corneal neoplasia in horses is rare. In most cases, tumours extend into the cornea from the adjacent limbus, sclera and/or conjunctiva with only a handful of cases described originating on the cornea. The most common tumour reported affecting the cornea is squamous cell carcinoma with other types of neoplasia described as sporadic case reports. This short clinical commentary accompanies and intends to complement a report of primary corneal lymphoma in a horse (Equine Vet Educ, 2022,https://doi.org/10.1111/eve.13601).
Insights into the ribosomal trans‐translation rescue system: lessons from recent structural studies
Authors: D’Urso Gaetano , Guyomar Charlotte , Chat Sophie , Giudice Emmanuel , Gillet Reynald
Published: January 2022

The arrest of protein synthesis caused when ribosomes stall on an mRNA lacking a stop codon is a deadly risk for all cells. In bacteria, this situation is remedied by the trans‐translation quality control system. Trans‐translation occurs because of the synergistic action of two main partners, transfer‐messenger RNA (tmRNA) and small protein B (SmpB). These act in complex to monitor protein synthesis, intervening when necessary to rescue stalled ribosomes. During this process, incomplete nascent peptides are tagged for destruction, problematic mRNAs are degraded and the previously stalled ribosomes are recycled. In this ‘Structural Snapshot’ article, we describe the mechanism at the molecular level, a view updated after the most recent structural studies using cryo‐electron microscopy.
Impact of annealing treatment on the fatigue behavior of Inconel 625 produced by laser‐based powder bed fusion
Authors: Martin Noémie , Hor Anis , Copin Etienne , Lours Philippe , Ratsifandrihana Léon
Published: January 2022

Laser‐based powder bed fusion (LPBF) is attractive to build complex parts in spite of the low machinability of Inconel 625. The LPBF microstructures and tensile properties are well documented in literature. But fatigue properties and impact of the LPBF intrinsic defects and microstructures on the crack initiation and propagation mechanisms are uncommon. Low and high‐cycle fatigue tests at room and service temperature presented in this paper prove that the LPBF defects shorten the crack initiation stage. After annealing heat treatment, the microstructure adapts to the defects, and the fatigue response becomes similar to a free defect material. The fatigue life of as‐built Inconel 625 is lower than 50% of its monotonic yield tensile strength (YTS) while the annealed material reaches 100% of its YTS. The propagation rate is slowed by the homogeneous annealed microstructure and improved ductility resulting from removal of dislocation cells and changes in grain morphology.
Multi‐decadal changes in phytoplankton biomass in northern temperate lakes as seen through the prism of landscape properties
Authors: Paltsev Aleksey , Creed Irena F.
Published: January 2022

Ecologists collectively predict that climate change will enhance phytoplankton biomass in northern lakes. Yet there are unique variations in the structures and regulating functions of lakes to make this prediction challengeable and, perhaps, inaccurate. We used archived Landsat TM/ETM+ satellite products to estimate epilimnetic chlorophyll‐a (Chl‐a) concentration as a proxy for phytoplankton biomass in 281 northern temperate lakes over 28 years. We explored the influence of climate (air temperature, precipitation) and landscape proxies for nutrient sources (proportion of wetlands in a contributing catchment, size of the littoral zone, potential for wind‐driven sediment resuspension as estimated by the dynamic ratio) or nutrient sinks (lake volume) in a random forest model to explain heterogeneity in peak Chl‐a. Lakes with higher Chl‐a (median Chl‐a = 2.4 μg L−1, n = 40) had smaller volumes (<44 × 104 m3) and were more sensitive to increases in temperature. In contrast, lakes with lower Chl‐a (median Chl‐a = 0.6 μg L−1, n = 241) had larger volumes (≥44 × 104 m3), contributing catchments with smaller proportions of wetlands (<4.5% of catchment area, n = 70), smaller littoral zones (<16.4 ha, n = 137), minimal wind‐driven sediment resuspension (as defined by the dynamic ratio; <0.45, n = 232), and were more sensitive to increases in precipitation. Lakes with larger volumes were generally less responsive to climate factors; however, larger volume lakes with a significant proportion of wetlands and larger littoral zones behaved similarly to lakes with smaller volumes. Our finding that lakes with different landscape properties respond differently to climate factors may help predict the susceptibility of lakes to eutrophication under changing climatic conditions.
Differential regulation of p27Kip1 depending on culture conditions and its correlation with status of p14ARF and p53
Authors: Kometani Tatsuya , Kawasaki Yutaro , Chibazakura Taku
Published: January 2022

p27Kip1 is known as a major cyclin‐dependent kinase inhibitor and a tumor suppressor, and often functionally hampered at protein level. p27 protein expression levels are frequently low in various cancers and negatively correlated with malignancy of cancer. However, in our previous study, we discovered that p27 overexpression does not inhibit the proliferation of two cancer cell lines due to a functional suppression of p27 by nucleophosmin isoform 1 (NPM1); that is, a qualitative, not quantitative, suppression of p27 function occurs in these cancer cell lines. To clarify the regulation of p27 in several types of cancer, we investigated p27 function in other cancer cell lines, based on proliferation assays in those cell lines carrying doxycycline‐inducible p27, and found that MDAH041 cells which express p14ARF, an antagonist of NPM1, show growth inhibition depending on p27 induction. Moreover, to investigate p27 function under anchorage‐independent culture conditions, we performed soft agar colony formation assay and observed that the colony formation of some cell lines carrying wild‐type p53, a major tumor suppressor, was inhibited depending on p27 induction. These results suggest that p27 function is regulated differentially among cancer cell types under anchorage‐dependent and anchorage‐independent culture conditions.
Perceived barriers and facilitators to exercise in kidney transplant recipients: A qualitative study
Authors: Billany Roseanne E. , Smith Alice C. , Stevinson Clare , Clarke Amy L. , Graham‐Brown Matthew P. M. , Bishop Nicolette C.
Published: January 2022

Background

Exercise has the potential to attenuate the high levels of cardiovascular morbidity and mortality present in kidney transplant recipients (KTRs). Despite this, activity levels in KTRs remain low. The aim of this qualitative study was to explore the barriers and facilitators of exercise in KTRs.

Methods

Thirteen KTRs (eight males; mean ± SD; age 53 ± 13 years; estimated glomerular filtration rate 53 ± 21 ml/min/1.73 m2) were recruited and completed semistructured one‐to‐one interviews at University Hospitals of Leicester NHS Trust. All KTRs were eligible if their kidney transplant was completed >12 weeks before interview and their consultant considered them to have no major contraindications to exercise. All interviews were audio recorded, transcribed verbatim and subject to framework analysis to identify and report themes.

Results

Themes were organized into personal, behavioural and environmental factors based on social cognitive theory. Facilitators of exercise were largely internal: enjoyment, exercise for general health and health of the transplanted kidney and desire to maintain normality. Social interaction, support and guidance of healthcare professionals and goal setting were perceived as motivational. Harming the kidney, a lack of guidance, self‐motivation and accessibility were barriers to exercise.

Conclusion

These results provide detailed insight into the development of interventions designed to increase physical activity in KTRs. They provide strong evidence that specific exercise guidelines are required for this population and that the healthcare system could have a key role in supporting KTRs to become more physically active. Interventions need to be multifaceted to appeal to the differing levels of support desired by KTRs.

Patient or Public Contribution

KTRs were involved in the development of the interview topic guide to ensure all relevant topics were explored.
Positive Outcomes: Validity, reliability and responsiveness of a novel person‐centred outcome measure for people with HIV
Authors: Harding Richard , Jones Christopher Iain , Bremner Stephen , Bristowe Katherine , West Brian , Siegert Richard J. , O’Brien Kelly K. , Whetham Jennifer ,   EMERGE Consortium, Horizon 2020
Published: January 2022

Objectives

Despite successful treatment, people living with HIV experience persisting and burdensome multidimensional problems. We aimed to assess the validity, reliability and responsiveness of Positive Outcomes, a patient‐reported outcome measure for use in clinical practice.

Methods

In all, 1392 outpatients in five European countries self‐completed Positive Outcomes, PAM‐13 (patient empowerment), PROQOL‐HIV (quality of life) and FRAIL (frailty) at baseline and 12 months. Analysis assessed: (a) validity (structural, convergent and divergent, discriminant); (b) reliability (internal consistency, test‐retest); and (c) responsiveness.

Results

An interpretable four‐factor structure was identified: ‘emotional wellbeing’, ‘interpersonal and sexual wellbeing’, ‘socioeconomic wellbeing’ and ‘physical wellbeing’. Moderate to strong convergent validity was found for three subscales of Positive Outcomes and PROQOL (ρ = −0.481 to −0.618, all p < 0.001). Divergent validity was found for total scores with weak ρ (−0.295, p < 0.001). Discriminant validity was confirmed with worse Positive Outcomes score associated with increasing odds of worse FRAIL group (4.81‐fold, p < 0.001) and PAM‐13 level (2.28‐fold, p < 0.001). Internal consistency for total Positive Outcomes and its factors exceeded the conservative α threshold of 0.6. Test‐retest reliability was established: those with stable PAM‐13 and FRAIL scores also reported median Positive Outcomes change of 0. Improved PROQOL‐HIV score baseline to 12 months was associated with improved Positive Outcomes score (r = −0.44, p < 0.001).

Conclusions

Positive Outcomes face and content validity was previously established, and the remaining validity, reliability and responsiveness properties are now demonstrated. The items within the brief 22‐item tool are designed to be actionable by health and social care professionals to facilitate the goal of person‐centred care.
Gamma radiation shielding studies on highly dense barium bismuth borate glasses
Authors: Chinthakayala Sai Kumar , Gadige Paramesh , Kollipara Vijay Sai , Ramadurai Gowrishankar
Published: January 2022

Transparent dense barium bismuth borate (BBB) glasses in ternary x(BaO–Bi2O3)–(1–x)B2O3 system, with x = .15, .25, .35, and .45, were prepared by the melt‐quenching process. Density of the glasses increased to 7.145 g/cm3 with increasing BaO–Bi2O3 content. Gamma radiation shielding performance of the glasses was estimated by studying mass attenuation coefficients (MAC) and effective atomic numbers, using XCOM software as a function of photon energy. Subsequently, experimental MAC values of the glasses were measured using 152Eu and 60Co sources by the radiation transmission method. Measured and calculated MAC values of the glasses were in close agreement. Equivalent atomic numbers, exposure, and energy absorption buildup factors were analyzed at different mean free paths and photon energies using Phy‐X software. Dense glasses exhibited large effective atomic numbers and radiation shielding characteristics comparable with the dense heavy metal oxide glasses. Effective atomic numbers of the glasses were found to be close to the heavy metallic elements (Pb, W, and Hf) at low gamma energies. Radiation shielding ability of the glasses is discussed by comparing with the recently reported radiation shielding glasses and conventional shielding materials. Lead‐free and dense transparent BBB glasses in the present study can be effective in radiation shielding for radiological applications.
Effectiveness of an adapted physical activity intervention for weight management in adolescents with intellectual disability: A randomized controlled trial
Authors: Yu Siyue , Gao Yang , Wang Aiwei , Sun Yan , Wang Jingjing , Kwok Heather Hei Man , Wu Shing , Lam Chi Kei , Tao Emma Dan , Jiao Jojo Jiao , Fong Shirley Siu Ming , Xie Yaojie , Zhang Dexing , Baker Julien S.
Published: January 2022

Objective

To evaluate the effectiveness of a 9‐month school‐based adapted physical activity (APA) program for reducing weight among adolescents with intellectual disability (ID).

Methods

In this randomized controlled trial, adolescents with ID, aged 12–18 years, who were overweight/or with obesity were randomly assigned into intervention and control groups. The APA intervention consisted of aerobic and resistance exercises with an overall moderate intensity and was delivered at a frequency of two sessions per week for 9 months. Changes in body mass index (BMI, primary outcome) and changes in BMIz, weight, percent body fat, waist circumference and waist‐to‐height ratio (secondary outcomes) were examined using general linear models.

Results

In total 61 subjects (39 in the intervention and 22 in the control) completed the study and were included in the analyses. At 9 months, the intervention group exhibited a reduced BMI of −0.66 kg/m2 (95% CI −1.06 to −0.25 kg/m2, p = 0.002), while a significant increase in BMI was observed in the control group. A significant post‐intervention between‐group difference in change in BMI (−1.31 kg/m2 [95% CI −1.99 to −0.63], p < 0.01) was found in favour of the intervention group. Similar results were also observed for all secondary outcomes.

Conclusions

This study provides evidence that a 9‐month APA intervention induced clinically meaningful effects on weight loss in adolescents with ID.
Experts as researchers and policy actors: Czech pension reform
Authors: Potůček Martin
Published: January 2022

Is it possible to act simultaneously as an expert and co‐policymaker without breaking the rules for knowledge‐based social policies? Trying to answer this question, I recap my experience as Chairman of the Czech Government‐established Expert Committee on Pension Reform in 2013–2017. I reflected on it analysing and advising on the path of the Czech pension reform. Applying theories of actor‐centred and discursive institutionalism, I analysed the rich empirical evidence based on the content of manyfold actors’ discourses. My involvement gave me a chance to participatorily observe the behaviour of formal and informal actors and thus learn more about their ideological positions, communication and negotiation strategies, and final embodiments of these disputes in policy proposals and acts. I analysed the roles of experts as moderators of discourse, analysts, and policy actors themselves. Following this experience, I offer some tentative conclusions for further discussion.
Enhancing giant dielectric properties of Ta5+‐doped Na1/2Y1/2Cu3Ti4O12 ceramics by engineering grain and grain boundary
Authors: Saengvong Pariwat , Chanlek Narong , Srepusharawoot Pornjuk , Harnchana Viyada , Thongbai Prasit
Published: January 2022

Various strategies to improve the dielectric properties of ACu3Ti4O12 (A = Sr, Ca, Ba, Cd, and Na1/2Bi1/2) ceramics have widely been investigated. However, the reduction in the loss tangent (tanδ) is usually accompanied by the decreased dielectric permittivity (ε′), or vice versa. Herein, we report a route to considerably increase ε′ with a simultaneous reduction in tanδ in Ta5+–doped Na1/2Y1/2Cu3Ti4O12 (NYCTO) ceramics. Dense microstructures with segregation of Cu– and Ta–rich phases along the grain boundaries (GBs) and slightly increased mean grain size were observed. The samples prepared via solid‐state reaction displayed an increase in ε′ by more than a factor of 3, whereas tanδ was significantly reduced by an order of magnitude. The GB–conduction activation energy and resistance raised due to the segregation of Cu/Ta–rich phases along the GBs, resulting in a decreased tanδ. Concurrently, the grain–conduction activation energy and grain resistance of the NYCTO ceramics were reduced by Ta5+ doping ions owing to the increased Cu+/Cu2+, Cu3+/Cu2+, and Ti3+/Ti4+ ratios, resulting in enhanced interfacial polarization and ε′. The effects of Ta5+ dopant on the giant dielectric response and electrical properties of the grain and GBs were described based on the Maxwell–Wagner polarization at the insulating GB interface, following the internal barrier layer capacitor model.
A rare variant of obstructed hemivagina and ipsilateral renal agenesis and its improvement of classification
Authors: Feng Tongfu , Rao Xiaoyan , Yang Xiaohong , Yu Xudong , Xia Feng , Du Xin
Published: January 2022

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) is a rare congenital malformation of the female reproductive organs, including uterine dysplasia, blind hemivagina, and ipsilateral renal dysplasia. It has a serious impact on patients' quality of life and fertility. We report a rare case of OHVIRA with a complete septate uterus, ectopic dysplasia of the left kidney, left ectopic ureter, and three oblique vaginal septa. The dysplastic left kidney and the ectopic ureter were removed during laparoscopy. In addition, the two layers of vaginal septa, which were ignored in the past 10 years, were removed by hysteroscopy. As the detection rate of OHVIRA has gradually increased, manifestations that previous classification systems could not recapitulate have emerged. By retrieving the relevant cases, we have tried to propose a new classification system, which would allow clinicians to have a complete understanding of the manifestations of OHVIRA and would be helpful in the treatment of patients.
The impact of underutilization of preventive dental care by adult Medicaid participants
Authors: Okunev Ilya , Tranby Eric P. , Jacob Matt , Diep Vuong K. , Kelly Abigail , Heaton Lisa J. , Frantsve‐Hawley Julie
Published: January 2022

Objective

To ascertain the financial impact associated with the underutilization of preventive dental care for adults enrolled in Medicaid.

Methods

We used adult claims data for patients aged 21–64 in the IBM Watson Marketscan Medicaid database. Enrollees were included if they had at least one dental claim in 2019 and were continuously enrolled between 2014 and 2019. We then evaluated the costs of their dental care in 2019, based on the number of years of preventive dental care they received between 2014 and 2018. We also assessed Emergency Department (ED) utilization for dental conditions, oral surgeries, and dental‐related opioid prescriptions.

Results

The average Medicaid enrollee with five continuous years of preventive care prior to 2019 experienced 43% lower costs than an individual who received no preventive dental care at all. Most of the savings were a result of fewer oral surgeries. A Medicaid enrollee with no preventive dental visits was eight times more likely to have an ED visit for a nontraumatic dental condition (NTDC), seven times more likely to have oral surgery and six times more likely to receive a dental‐related opioid prescription compared to those who had a dental prevention visit every year in the 5‐year lookback period.

Conclusions

Regular preventive dental care in the lookback period was associated with significant savings in overall dental care costs when compared to dental care costs for those individuals who received no or few preventive visits. Prior preventive dental care was also associated with lower rates of ED‐NTDC utilization, oral surgery, and dental‐related opioid prescriptions.
Undoing structural racism in dentistry: Advocacy for dental therapy
Authors: Bianchi Tera , Wilson Kasey , Yee Albert
Published: January 2022

Like other areas of health, structural racism has a deep impact on oral health and is a key driver of racial inequities in access to care and outcomes. Racism also structures the relationship between oral health and access to economic opportunities. As a result, communities of color, American Indian/Alaska Native (AI/AN) communities, and low‐income populations experience the highest rates of the health, social, and economic costs of dental disease. This is compounded by issues of community‐level dental fear/trauma resulting from receiving itinerate care. Dentistry has long struggled to equitably distribute care and diversify its overwhelmingly white and affluent workforce, resulting in many communities not having access to providers who represent their identity and/or live in their community. While multi‐generational lack of access to dental care is not unique to Alaska, Alaska Native communities are the home to a reimagined, community‐centered care delivery system that is improving health outcomes. For almost two decades, AI/AN leaders have recruited and trained community members to serve as dental therapists—dental team members who offer routine and preventive care responsive to local geographic and cultural/community norms. As members of the communities they serve, dental therapists are fluent in the language and cultural norms of their patients, improving patient‐provider trust, access to care, and oral health outcomes. The communities that dental therapists serve are also now investing money and training in their community members, building educational opportunities, and professional wage jobs and directly countering the economic impact structural racism has on oral health.
Artificial urethral sphincter in male dogs with urethral sphincter mechanism incompetence: 19 cases (2010–2017)
Authors: Bohlen M. , Nickel R.
Published: January 2022

Objective

To assess the outcome and safety of surgically placed artificial urethral sphincters in male dogs with urethral sphincter mechanism incompetence.

Materials and Methods

We included dogs with urethral sphincter mechanism incompetence treated by placing an artificial urethral sphincter from January 1, 2010 to December 31, 2017. The continence score (scale 1 to 5, with 5 indicating complete continence) was evaluated before and after implantation. Follow‐up information was obtained from the institution's medical records (short‐term up to 12 months) and questionnaires were completed by telephone (long‐term ≥12 months) for evaluation.

Results

Medical therapy was unsuccessful in 18 dogs and unknown in one dog before the artificial urethral sphincter placement. Short‐term continence improved in 16 of the 19 (84%) dogs. Four patients were lost to follow‐up. Nine of 15 (60%) dogs showed long‐term continence improvement, eight of 15 (53%) remained completely continent. The median follow‐up was 1785 (range 2 to 3234) days. The complication rate was 56% (9/16). Minor complications, including haematoma, stranguria/temporary dyssynergia and mild inflammation at the port, were reported in four of 16 (25%) dogs. Five of 16 (31%) experienced major complications, including stranguria/mechanical urethral obstruction, persistent dyssynergia, fistula at the port and port rotation.

Clinical Significance

Artificial urethral sphincter placement is a valid option for treating incontinent male dogs that show an insufficient response or become refractory to medical or other prior surgical management. A high‐complication rate is associated with this procedure.
When I say… health advocacy
Authors: Hubinette Maria M. , LaDonna Kori A. , Scott Ian , van der Goes Theresa , Kahlke Renate
Published: January 2022

When Hubinette et al. say 'health advocacy' they encourage a broad view that invites opportunities to address social and structural determinants of health, enabling physicians to be agents of change.