bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Capital and Investment: Evidence from 2012 Pension Relief*
Authors: Kubick Thomas R. , Lockhart G. Brandon , Robinson John R.
Published: March 2021

We use changes in mandatory pension funding to investigate the relation between internal financing constraints and incremental investment. Pension funding relief enacted in 2012 significantly reduced mandatory employer contributions to defined benefit pension plans. Prior to learning of the pension relief, firms disclosed their expected pension contributions under FAS 132R, which allows us to infer changes in investment plans in response to this unanticipated pension relief. Although our setting is pensions, our inferences contribute to the broader literature on how access to finance impacts the firm. We predict and find that pension relief resulted in increased nonpension investment in the year after enactment for financially constrained firms, and is stronger for constrained firms with greater pension underfunding. Our results are consistent with pension relief providing an important means of funding investment for financially constrained firms. Our identification strategy and results provide an important innovation to the literature examining the effect of financing constraints on investment.
Common Mutual Fund Ownership and Systemic Risk*
Authors: Iselin Michael , Liao Scott , Zhang Haiwen (Helen)
Published: March 2021

We examine whether bank connections via common mutual fund ownership serve as a contagion channel affecting the systemic risk of the banking system. Examining this relation is important because common mutual fund ownership has increased dramatically over the past 20 years, and a buildup of systemic risk was at the heart of the 2008–2009 financial crisis. We predict and document that the extent of a bank's connection with other banks via common ownership increases its contribution to systemic risk. We further predict and find that this association is primarily driven by passive mutual funds. We provide evidence that common passive ownership results in higher systemic risk through two mechanisms: nondiscretionary sell‐offs of bank stocks and a common pattern of voting. Our results are also robust to two alternate instrumental variable analyses. This study contributes to the literature by documenting an unintended, macro‐level consequence of common mutual fund ownership. Our findings broaden the understanding of common ownership as one mechanism through which systemic risk materializes and should be particularly relevant for regulators who seek to prevent future systemic failures.
The influence of physical–chemical variables on phytoplankton and lesser flamingo (Phoeniconaiasminor) abundances in Lake Natron, Tanzania
Authors: Mgimwa Emmanuel F. , John Jasson R. , Lugomela Charles V.
Published: March 2021

Soda lakes are alkaline ecosystems characterised by extreme conditions and are one of the most productive aquatic ecosystems. Lesser flamingo, an obligate phytoplankton filter feeder, is widely identified as the flagship species of these saline‐alkaline wetlands throughout the African continent. This study, carried out at three lagoons in Lake Natron for ten consecutive months from March 2019, investigated the relationship between Chlorophyll‐a and lesser flamingo abundances, and physical–chemical variables and Chlorophyll‐a abundance. Lake Natron is the only regular breeding site for the East African population of this specialised species and is known to host thousands of birds year‐round. There was a strong correlation between lesser flamingo and Chlorophyll‐a abundances. Chlorophyll‐a abundance was significantly influenced by dissolved oxygen, water turbidity, phosphate, nitrate and ammonium. Findings from this study suggest that annual fluctuation in the lesser flamingos numbers in Lake Natron is triggered by phytoplankton abundance whose primary productivity is influenced by physical–chemical variables in the lake waters. In turn, these changes are mainly due to both anthropogenic activities and weather changes within the lake basin and its surroundings. Thus, the conservation and management of this lake require concerted efforts from different stakeholders including those found in Kenya.
Beneficiaries of Forest Carbon: Precarious Inclusion in the Brazilian Amazon
Authors: Greenleaf Maron
Published: March 2021

Sustainable development projects and progressive politics of all kinds emphasize inclusion. Sometimes inclusion is meant to occur through giving benefits to poorer people, who are then governed as “beneficiaries.” But what does it mean to be a beneficiary? I examine this question through analyzing climate‐motivated forest‐protection efforts in the Amazonian state of Acre, Brazil, that distribute benefits to poorer smallholders. This environmentally premised redistribution connects beneficiaries to the state, engendering a form of benefits‐based citizenship and everyday spaces for negotiating its meaning. Whereas the state positions the beneficiary as a temporary status, beneficiaries envision it as a long‐term relationship based on an exchange: state benefits given in exchange for them forgoing deforestation. Some beneficiaries use their new inclusion to assert this mutual dependence and claim more from the state. The increase in Amazonian deforestation threatens forest beneficiaries’ already precarious inclusion. [distribution, climate change, precarity, deforestation, Amazon]
Male seminal parameters are not associated with Leydig cell functional capacity in men
Authors: Anand‐Ivell Ravinder , Tremellen Kelton , Soyama Hiroaki , Enki Doyo , Ivell Richard
Published: March 2021

Background

Insulin‐like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiation status of these steroidogenic cells and lacks the biological and technical variance of the steroid testosterone. This retrospective study was carried out to examine the relationship between seminal parameters and the Leydig cell compartment, and secondarily to assess other factors responsible for determining Leydig cell functional capacity.

Methods

INSL3 was assessed together with seminal, anthropometric, and hormonal parameters in a Swedish cohort of 18‐year‐old men, representing the average population, and in a smaller, more heterogeneous cohort of men visiting an Australian infertility clinic.

Results and discussion

Average INSL3 concentration at 18 years is greater than that reported at younger or older ages and indicated a large 10‐fold variation. In neither cohort was there a relationship between INSL3 concentration and any semen parameter. For the larger, more uniform Swedish cohort of young men, there was a significant negative relationship between INSL3 and BMI, supporting the idea that adult Leydig cell functional capacity may be established during puberty. In both cohorts, there was a significant relationship between INSL3 and FSH, but not LH concentration. No relationship was found between INSL3 and androgen receptor trinucleotide repeat polymorphisms, reinforcing the notion that Leydig cell functional capacity is unlikely to be determined by androgen influence alone. Nor did INSL3 correlate with the T/LH ratio, an alternative measure of Leydig cell functional capacity, supporting the view that these are independent measures of Leydig cell function.
Management of major obstetric hemorrhage prior to peripartum hysterectomy and outcomes across nine European countries
Authors: Kallianidis Athanasios F. , Maraschini Alice , Danis Jakub , Colmorn Lotte B. , Deneux‐ Tharaux Catherine , Donati Serena , Gissler Mika , Jakobsson Maija , Knight Marian , Kristufkova Alexandra , Lindqvist Pelle G. , Vandenberghe Griet , van den Akker Thomas ,   INOSS (the International Network of Obstetric Survey Systems)
Published: March 2021

Introduction

Peripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy.

Material and methods

We merged data from nine nationwide or multi‐regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated.

Results

A total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births.

Conclusions

Management of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life‐saving procedure is associated with substantial adverse maternal and neonatal outcome.
Variance reduction in the inverse probability weighted estimators for the average treatment effect using the propensity score
Authors: Liao Jiangang , Rohde Charles
Published: March 2021

The propensity methodology is widely used in medical research to compare different treatments in designs with a nonrandomized treatment allocation. The inverse probability weighted (IPW) estimators are a primary tool for estimating the average treatment effect but the large variance of these estimators is often a significant concern for their reliable use in practice. Inspired by Rao‐Blackwellization, this paper proposes a method to smooth an IPW estimator by replacing the weights in the original estimator by their mean over a distribution of the potential treatment assignment. In our simulation study, the smoothed IPW estimator achieves a substantial variance reduction over its original version with only a small increased bias, for example two‐to‐sevenfold variance reduction for the three IPW estimators in Lunceford and Davidian [Statistics in Medicine, 23(19), 2937–2960]. In addition, our proposed smoothing can also be applied to the locally efficient and doubly robust estimator for added protection against model misspecification. An implementation in R is provided.
Factor VIII levels and bleeding according to factor 8 (F8) mutation in pregnant carriers of haemophilia A: a multicentre retrospective cohort study
Authors: Collins Annie E. I. , Curry Nicola , Raza‐Burton Sayma , Bignell Patricia , Davies Claire , Joffe Michael , Shapiro Susan , Desborough Michael J. R.
Published: March 2021

This retrospective cohort study investigated the association between factor 8 (F8) genotype severity and factor VIII (FVIII) levels during pregnancy for 52 women (64 pregnancies) who were heterozygous carriers of mild, moderate or severe haemophilia A. There were no significant differences in FVIII levels for carriers of mild, moderate or severe haemophilia A at baseline [mean (SD) level: mild, 0·78 (0·22); moderate, 0·83 (0·33); severe, 0·70 (0·25) iu/ml; P = 0·81] or in the third trimester [mean (SD) level: mild, 1·42 (0·28); moderate, 1·47 (0·41); severe, 1·37 (0·49) iu/ml; P = 0·80). Post‐partum haemorrhage rates were higher for carriers of severe haemophilia A (13/24; 54·2%) compared to carriers of mild haemophilia A (four of 14; 28·6%).
Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease
Authors: Mikhailova Ekaterina , Semchenkova Alexandra , Illarionova Olga , Kashpor Svetlana , Brilliantova Varvara , Zakharova Elena , Zerkalenkova Elena , Zangrando Andrea , Bocharova Natalia , Shelikhova Larisa , Diakonova Yulia , Zhogov Vladimir , Khismatullina Rimma , Molostova Olga , Buldini Barbara , Raykina Elena , Larin Sergey , Olshanskaya Yulia , Miakova Natalia , Novichkova Galina , Maschan Michael , Popov Alexander M.
Published: March 2021

CD19‐directed treatment in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP‐ALL is based on B‐cell compartment study, CD19 loss could hamper MFC‐MRD monitoring after blinatumomab or chimeric antigen receptor T‐cell (CAR‐T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B‐lineage gating markers allows the identification of CD19‐negative leukaemia, but it could also lead to misidentification of normal very‐early CD19‐negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19‐negative normal BCPs in 106 children with BCP‐ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR‐T, n = 25; or both, n = 17). It was found that normal CD19‐negative BCPs could be found in bone marrow after CD19‐directed treatment more frequently than in healthy donors and children with BCP‐ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19‐negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC‐MRD more accurately in patients who have undergone CD19‐targeted therapy, even in cases with normal CD19‐negative BCP expansion.
Resolving the small‐pockets problem helps clarify the role of education and political ideology in shaping vaccine scepticism
Authors: Hornsey Matthew J. , Edwards Martin , Lobera Josep , Díaz‐Catalán Celia , Barlow Fiona Kate
Published: March 2021

Understanding the factors associated with vaccine scepticism is challenging because of the ‘small‐pockets’ problem: The number of highly vaccine‐sceptical people is low, and small subsamples such as these can be missed using traditional regression approaches. To overcome this problem, the current study (N = 5,200) used latent profile analysis to uncover six profiles, including two micro‐communities of vaccine‐sceptical people who have the potential to jeopardize vaccine‐led herd immunity. The most vaccine‐sceptical group (1.14%) was highly educated and expressed strong liberal tendencies. This group was also the most sceptical about genetically modified crops and nuclear energy, and most likely to receive news about science from the Internet. The second‐most vaccine‐sceptical group (3.4%) was young, poorly educated, and politically extreme (both left and right). In resolving the small‐pockets problem, the current analyses also help reconcile competing theoretical perspectives about the role of education and political ideology in shaping anti‐vaccination views.
Microfinance and missing markets
Authors: Shahe Emran M. , Mahbub Morshed A. K. M. , Stiglitz Joseph E.
Published: March 2021

The existing theoretical analysis of microfinance focuses on the nature of the loan contract such as group liability. We draw attention to the role of missing or imperfect labour markets in understanding some of the important “second generation” debates in microfinance. Our analysis helps explain a number of puzzles in microfinance including high repayment rates with high interest rates, difficulties in scaling up projects, limited economic impact on borrowing households, low take‐up rates in recent microcredit programs, conflicting views about the interest rate elasticity of demand, and spurious mission drift. Microcredit can play a role when labour markets are underdeveloped, but it may also hinder structural transformation.
The frequency of interleukin-1β-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents
Authors: Picard E , Bowdish D M E , McElhaney J E , Pawelec G , Loeb M , Verschoor C P
Published: March 2021

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80–99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1β, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1β+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1β+ CD14+ monocytes were significant mediators of the associations between IL-1β and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1β+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.
A critical review of qualitative research publications in dental implants from 2006 to 2020
Authors: Jayachandran Sivakumar , Hill Kirsty , Walmsley Anthony Damien
Published: March 2021

Objectives

This critical review is aimed to investigate the current status of qualitative research in dental implant research and to explore the quality of available information.

Material and methods

A systematic search was done on the journal databases to identify dental implant research articles that used qualitative methodology during 2006 and 2020. The resulting articles were appraised against the checklist offered by the Critical Appraisal Skills programme (CASP) tool. Also, the theories evolved from the research were reviewed to understand the value of this methodology in dental implant research.

Results

Twenty‐five (25) articles out of the 8,421 original results were identified as using qualitative methodology. The researchers have sought to identify the views of patients about tooth loss, dental implants, and the information they receive from dental professionals, and views of the dentists about dental implant practice. The review found that there were few inconsistencies in the quality of such research especially the qualitative data analysis.

Conclusions

The quantity of qualitative research in dental implants remains low; however, the quality has improved in the past two decades. Despite these improvements, there is still a lack of research in understanding both patients’ and dentists’ views on dental implant procedures and management.
Early implant placement in ridge preserved extraction sockets: A pre‐clinical in vivo study
Authors: Rodriguez‐Ortiz Gabriel , Chen Stephen , Davies Helen , Fitzgerald Wayne , Darby Ivan
Published: March 2021

Objectives

The aim was to analyse the outcomes of early implant placement after 6 and 12 weeks of healing in ridge preserved sites in a canine model.

Materials and methods

Implants were placed in second maxillary incisors sites in 9 dogs 6 weeks after grafting of the sockets with 90% deproteinized bovine bone mineral in 10% collagen matrix (DBBMC) and closure with resorbable type I/III porcine collagen matrix (PCM). The implants were randomly assigned to 6 (T6) and 12 (T12) weeks of healing.

Results

The percentage of bone‐to‐implant contact (%BIC), old bone, new bone and residual DBBMC was similar between T6 and T12. In relation to the implant shoulder (IS), the original bone crest (IS‐ROB) was more apical on the buccal than the palatal side. The regenerated bone crest (IS‐C) and IS‐ROB were similar between groups. However, the distance from IS to first bone‐to implant contact (IS‐fBIC) was significantly less in T12 compared with T6 (p = .022; Wilcoxon signed‐rank test). The bucco‐palatal ridge dimensions between T6 and T12 were similar.

Conclusions

This study confirms that implants can successfully be placed early in ridge preserved maxillary second incisor sites and are osseointegrated by 6 weeks. There were significantly lower IS‐fBIC values at 12 weeks than at 6 weeks on the buccal aspect. The original buccal bone crest underwent greater corono‐apical resorption than the palatal crest. The %BIC, relative proportions of mineralized tissues and dimensions of the alveolar ridge demonstrated stability between 6 and 12 weeks of healing.
Effect of biofilm formation on implant abutments with an anti‐bacterial coating: A pre‐clinical in vivo study
Authors: Almohandes Ahmed , Abrahamsson Ingemar , Dahlén Gunnar , Berglundh Tord
Published: March 2021

Objectives

To analyse the long‐term effect of plaque formation on implant abutments with an antibacterial coating and the ensuing host response in peri‐implant tissues.

Materials and methods

Four implants were installed in each mandibular premolar region following tooth extraction in six dogs. Three months later, two test abutments with a titanium–bismuth–gallium (Ti‐Bi‐Ga) coating and two control titanium abutments were connected to the implants on each side of the mandible. After 2 months, ligatures were placed around the implants in one side of the mandible and plaque formation was allowed until the end of the experiment. The ligatures were removed after 4 weeks. Radiographs and microbiological samples were obtained from each implant site during the plaque formation period. Biopsies were obtained 8 months after abutment connection and prepared for histological analysis.

Results

The analysis did not reveal any statistically significant differences in bone loss, bacterial growth and size of inflammatory lesions between implant units with and without the Ti‐Bi‐Ga coating. Implant sites exposed to the short period of ligature‐induced breakdown demonstrated more pronounced bone loss and bacterial growth than non‐ligature sites.

Conclusions

It is suggested that a Ti‐Bi‐Ga coating does not prevent biofilm formation on the implant device and does not influence the ensuing host response in the adjacent peri‐implant mucosa.
Delay to elective colorectal cancer surgery and implications for survival: a systematic review and meta‐analysis
Authors: Whittaker Thomas M , Abdelrazek Mohamed E. G. , Fitzpatrick Aran J. , Froud Joseph L. J. , Kelly Jack R. , Williamson Jeremy S. , Williams Gethin L.
Published: March 2021

Aim

The Covid‐19 pandemic has delayed elective colorectal cancer (CRC) surgery. The aim of this study was to see whether or not this may affect overall survival (OS) and disease‐free survival (DFS).

Method

A systematic review was carried out according to PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were interrogated. Patients aged over 18 years with a diagnosis of colon or rectal cancer who received elective surgery as their primary treatment were included. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Meta‐analysis of the outcomes OS and DFS were conducted. Forest plots, funnel plots and tests of heterogeneity were produced. An estimated number needed to harm (NNH) was calculated for statistically significant pooled hazard ratios (HRs).

Results

Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314 560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a 1 month delay, the HR for six datasets was 1.13 (95% CI 1.02–1.26, p = 0.020) and at 3 months the pooled HR for three datasets was 1.57 (95% CI 1.16–2.12, p = 0.004). The estimated NNH for a delay at 1 month and 3 months was 35 and 10 respectively. Delay was nonsignificantly negatively associated with DFS on meta‐analysis.

Conclusion

This review recommends that elective surgery for CRC patients is not postponed longer than 4 weeks, as available evidence suggests extended delays from diagnosis are associated with poorer outcomes. Focused research is essential so patient groups can be prioritized based on risk factors in future delays or pandemics.
Potential benefit of laparoscopic surgery for rectal cancer on postoperative male sexual function
Authors: Kondo Akihiro , Nishizawa Yuji , Tsukada Yuichiro , Sasaki Takeshi , Inoue Masaharu , Masuda Hitoshi , Suzuki Yasuyuki , Ito Masaaki
Published: March 2021

Aim

The aim of this retrospective study was to evaluate the incidence of male sexual dysfunction after mid to low rectal cancer surgery and to identify factors associated with postoperative erectile and ejaculatory dysfunction.

Methods

The subjects were 410 consecutive male patients who underwent surgery for mid to low rectal cancer from 2009 to 2015. Two questionnaires on sexual function were administered: the International Index of Erectile Function, and an original questionnaire on ejaculatory status. Erectile and ejaculatory dysfunction were examined before and 3, 6, 12 months after surgery. In patients without preoperative dysfunction, multivariate regression analyses were performed to identify factors associated with the incidence of erectile and ejaculatory dysfunction at 12 months after surgery.

Results

Of 410 patients, 234 (57%) gave complete responses to the questionnaires, of whom 108 (46%) and 155 (66%) had severe erectile dysfunction, while 115 (49%) and 168 (72%) had severe ejaculatory dysfunction before and 12 months after surgery, respectively. Of the patients who maintained sexual function preoperatively, the incidence of erectile and ejaculatory dysfunction at 12 months after surgery was 51% (64/126) and 49% (58/119), respectively. In multivariate analysis, age >60 years (P = 0.02), laparotomy (P = 0.002), and creation of a diverting ileostomy (P = 0.003) were independent factors associated with postoperative erectile dysfunction, while age >60 years (P = 0.005), laparotomy (P = 0.04), and lateral lymph node dissection (P = 0.001) were independent factors associated with postoperative ejaculatory dysfunction.

Conclusion

Sexual dysfunction occurred in almost half of patients after rectal cancer surgery, and was independently associated with several factors, including laparotomy.
Serum free light chains in solid organ transplant recipients
Authors: Kwapisz Dorota
Published: March 2021

Immunoglobulin is built by a pair of identical heavy and a pair of identical light chains. Light chains are produced in excess compared to heavy chains. Free light chains (FLCs) are those which are not combined with heavy chains. Currently, numerous assays are available for the measurement of serum FLCs (sFLCs). These assays cannot be used interchangeably, and renal function should be taken into account in interpreting test results. Levels of kappa and lambda sFLCs are usually used to diagnose and monitor plasma cell dyscrasias. However, the clinical relevance of sFLCs is being investigated in patients with a variety of diseases, including patients after transplantation. There are contradictory results regarding the usefulness of sFLCs in the prediction of post‐transplant lymphoproliferative disorder (PTLD). However, it seems that sFLCs may be helpful in the prediction of early‐onset PTLD. Some studies have shown that low levels of sFLCs are associated with a higher risk of infection in patients after transplantation. This review summarizes and highlights recent advances in the utility of sFLCs in the prediction of PTLD and infection, and inflammation assessment in patients after solid organ transplantation. Moreover, the influence of immunosuppressive treatment on sFLCs levels is described briefly.
Mitigating the negative impacts of aging on cognitive function; modifiable factors associated with increasing cognitive reserve
Authors: Amanollahi Mobina , Amanollahi Saba , Anjomshoa Ali , Dolatshahi Mahsa
Published: March 2021

Research suggests that social, physical, and cognitively challenging activities during lifetime, could mitigate the negative effects of aging on cognitive function. This effect is explained by the increased cognitive reserve (CR) resulting from such factors; in fact, such activities, by altering structural and functional properties of the human brain, equip one with more effective compensatory mechanisms to resist brain damage before the presentation of severe clinical symptoms. Therefore, applying appropriate modifications in one's lifestyle and activities may be effective in lowering the risk of developing dementia and cognitive dysfunction in old age, especially in brain areas that are susceptible to aging. In this paper, we are going to review relevant studies discussing the association between important modifiable factors, known as CR proxies (i.e., educational attainment, occupational complexity, physical activity, social engagement, bilingualism, leisure activities, and Mediterranean diet), and different domains of cognitive function, which are affected either in the process of healthy aging or neurodegenerative diseases.
Threat of shock promotes passive avoidance, but not active avoidance
Authors: Binti Affandi Aida Helana , Pike Alexandra C. , Robinson Oliver Joe
Published: March 2021

Anxiety and stress are adaptive responses to threat that promote harm avoidance. In particular, prior work has shown that anxiety induced in humans using threat of unpredictable shock promotes behavioral inhibition in the face of harm. This is consistent with the idea that anxiety promotes passive avoidance—that is, withholding approach actions that could lead to harm. However, harm can also be avoided through active avoidance, where a (withdrawal) action is taken to avoid harm. Here, we provide the first direct within‐study comparison of the effects of threat of shock on active and passive avoidance. We operationalize passive avoidance as withholding a button press response in the face of negative outcomes, and active avoidance as lifting/releasing a button press in the face of negative outcomes. We explore the impact of threat of unpredictable shock on the learning of these behavioral responses (alongside matched responses to rewards) within a single cognitive task. We predicted that threat of shock would promote both active and passive avoidance, and that this would be driven by increased reliance on Pavlovian bias, as parameterized within reinforcement‐learning models. Consistent with our predictions, we provide evidence that threat of shock promotes passive avoidance as conceptualized by our task. However, inconsistent with predictions, we found no evidence that threat of shock promoted active avoidance, nor evidence of elevated Pavlovian bias in any condition. One hypothetical framework with which to understand these findings is that anxiety promotes passive over active harm avoidance strategies in order to conserve energy while avoiding harm.
Deep phenotyping of an international series of patients with late‐onset dysferlinopathy
Authors: Fernández‐Eulate Gorka , Querin Giorgia , Moore Ursula , Behin Anthony , Masingue Marion , Bassez Guillaume , Leonard‐Louis Sarah , Laforêt Pascal , Maisonobe Thierry , Merle Philippe‐Edouard , Spinazzi Marco , Solé Guilhem , Kuntzer Thierry , Bedat‐Millet Anne‐Laure , Salort‐Campana Emmanuelle , Attarian Shahram , Péréon Yann , Feasson Leonard , Graveleau Julie , Nadaj‐Pakleza Aleksandra , Leturcq France , Gorokhova Svetlana , Krahn Martin , Eymard Bruno , Straub Volker ,   Jain COS Consortium, Evangelista Teresinha , Stojkovic Tanya
Published: March 2021

Background

To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.

Methods

Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.

Results

Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.

Conclusions

Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
The disappearance of ice cover on temperate lakes (Central Europe) as a result of climate warming
Authors: Ptak Mariusz , Sojka Mariusz
Published: March 2021

This paper presents changes in the ice regime of lakes located in the northern part of Poland. It has been established that in the period 1960–2019, there was a successive decline in the ice extent of lakes, clearly visible in individual parameters; formation of ice cover is delayed by 3.0 days/decade (on average for all lakes), its decline occurred earlier by 3.8 days/decade, and the length of ice cover is shorter by 6.8 days/decade. Moreover, the maximum thickness of the ice cover is becoming thinner, and this process has progressed at an average rate of 2.3 cm/decade. The aforementioned situation shows strong relations with air temperature. It was particularly evident in the late 1980s, when a change in the thermal regime took place, which was documented in most of the analysed parameters, as demonstrated in the study. It has been established that from that period up to now, the decline of ice cover tends to start 19 days earlier, the duration of ice cover is shorter by 22 days, and the ice cover is 8 cm thinner, on average. The observed transformation affects the imbalance of the existing equilibrium in lakes, which can be related to both biotic and abiotic processes.
A Comparative Plume Study of DRO, GRO, Benzene, and MTBE: Implications for Risk Management
Authors: O'Reilly Kirk , Lahvis Matthew A. , DeVaull George E. , Deines Andrew M.
Published: March 2021

Groundwater remediation and no‐further action decision making at petroleum underground storage tank (UST) sites has largely been based on an understanding of plume length, plume stability, and attenuation rates for key hydrocarbon constituents. Regulatory guidance to support and guide such decisions is based in part on plume studies involving individual hydrocarbon constituents, namely benzene and methyl tert‐butyl ether (MTBE). Questions remain regarding whether current guidance is applicable to chemical mixtures such as gasoline range organics (GRO), diesel range organics (DRO), and oxygen containing organic compounds (OCOCs) resulting from hydrocarbon biodegradation. To help address this concern, data from California's GeoTracker database were used to estimate maximum plume lengths, plume stability, and attenuation rates of DRO (which can be used as an analytical surrogate for OCOCs) and GRO relative to benzene and MTBE. The distributions of maximum plume lengths were similar for the four constituents with medians ranging from 27 to 32 m. The fraction of monitoring wells with a decreasing concentration trend ranged from 19% for DRO to 40% for MTBE, while fewer than 7% of the wells had an increasing concentration trend for any of the constituents. Median attenuation rates ranged from 0.10% day−1 for DRO to 0.17% day−1 for MTBE. The results suggest attenuation based risk management is appropriate for DRO and GRO plumes at most petroleum UST sites.
Histology‐based profile of inflammatory mediators in experimentally induced pulpitis in a rat model: screening for possible biomarkers
Authors: Li M. , Tian J. , Xu Z. , Zeng Q. , Chen W. , Lei S. , Wei X.
Published: March 2021

Aim

To profile molecular changes in lipopolysaccharide (LPS)‐induced experimental pulpitis in a rat model and explore the feasibility of a molecular‐based diagnostic strategy for pulpitis.

Methodology

Seventy‐three maxillary incisors of Sprague‐Dawley rats were used to establish pulpitis models with LPS. Inflammatory grading was performed in four equal sections of the pulp divided from the injured site to the root apex. An antibody array was used to compare the expression of 67 molecules between control pulp and inflamed pulp 12 and 72 h after LPS application. The levels of differentially expressed molecules in the control and inflamed pulp (collected at 3, 6, 9, 12, 24 and 72 h after LPS treatment) were examined via ELISA, and correlations between inflammatory scores and molecule expression were assessed. The molecule distributions in the pulp were investigated by immunofluorescence staining. Data were analysed with paired t‐test, one‐way anova, Kruskal–Wallis tests, and Spearman’s and Pearson’s correlations with significance set at P < 0.05.

Results

Polymorphonuclear neutrophils were observed in the injured site 3 h after LPS stimulation. Inflammatory infiltration peaked at 12 h and was limited to the injured site with osteodentine deposition at 72 h. Thirteen molecules were significantly differentially expressed between the control and LPS‐injured pulp. ELISA validated that tissue inhibitor of metalloproteinase‐1 (TIMP‐1) expression dramatically peaked at 12 h (compared with other time points, P < 0.05) and returned to baseline at 72 h. The TIMP‐1 concentration was strongly correlated with inflammation severity in the apical three‐quarters of the pulp, and the strongest correlation was found in the lower‐middle quarter (r = 0.786, P < 0.001). Immunofluorescence staining revealed that in the apical three‐quarters of the pulp, TIMP‐1 expression was significantly higher in the 12 h group than in the control and 3, 6, 24 and 72 h groups (P < 0.01).

Conclusion

This study provides a molecular profile of LPS‐induced pulpitis in a rat model. TIMP‐1 had a strong positive correlation with the severity of dental pulp inflammation, verifying the feasibility of applying biomarkers to identify specific pathological conditions in pulpitis.
Immature platelet fraction over time and clinical outcomes in patients with acute myocardial infarction
Authors: Yahud Ella , Schilo Tamar , Nevzorov Roman , Asher Elad , Bryk Gabriel , Laish‐Farkash Avishag , Lev Eli I.
Published: March 2021

Background

Immature platelets in the circulation can be measured as immature platelet fraction (IPF). Limited data exist regarding IPF during the course of an acute myocardial infarction (AMI), the association between IPF and extent of cardiac damage, and the long‐term prognostic implications of IPF in patients with AMI.

Aims

To examine the temporal course of IPF during the first month after AMI, the association between IPF and extent of cardiac damage, and the long‐term prognostic effect of IPF in AMI patients.

Methods

Patients with AMI treated with percutaneous coronary intervention (PCI) were examined. IPF was evaluated by a Sysmex XN‐3000 autoanalyzer, at 4 time points: baseline; one day post‐PCI; 3 days post‐PCI, and 30 days post‐PCI. The association between peak troponin‐T levels and IPF was evaluated. One‐year clinical outcomes (cardiac hospitalization, urgent revascularization, or death) were assessed.

Results

One hundred patients were included, mean age was 59.5 ± 11.3 years, 82 were men, 27 had diabetes, and 54 were hospitalized with ST‐segment elevation myocardial infarction (STEMI) and 46 with non‐ST segment elevation myocardial infarction (NSTEMI). The levels of IPF modestly decreased a day after PCI but did not change in subsequent measurements. Peak troponin‐T level was significantly associated with the levels of IPF at all 4 time points. IPF levels three days post‐PCI were associated with the composite clinical outcome at 1 year.

Conclusions

The levels of IPF following AMI remain relatively stable over a one‐month period. Higher levels of IPF during the acute phase of AMI appear to be associated with worse cardiac outcomes at 1 year.
Barriers to accessing mental health services in Somali‐Australian women: a qualitative study
Authors: Said Mulki , Boardman Gayelene , Kidd Susan
Published: March 2021

Despite the global prevalence of mental disorders being widely acknowledged, mental illness, complex trauma and the significant impact on individuals, families and communities continues to be poorly recognized, under‐diagnosed and underreported. Based on the 2017 Australian census, one‐in‐five (20%) people have experienced some type of mental illness within the last 12 months (Australian Bureau of Statistics [ABS], 2019). The prevalence rate of mental illness in culturally and linguistically diverse (CALD) communities is difficult to estimate due to cultural and linguistic issues and underutilization of mental health services. In particular, little epidemiological data is available about the prevalence of mental illness in the Somali‐Australian community. The aim of this study was to identify the perceived barriers to help‐seeking for mental health for Somali‐Australian women. A qualitative descriptive study incorporating focus group discussions with 31 Somali‐Australian women was conducted in Melbourne, Australia. Braun & Clarke’s (2006) thematic analysis was applied to the data. Four themes relating to help‐seeking barriers were abstracted. Influence of faith explored how Islam can impact the person views on mental illness. Stigma focused on the relationship between public and self‐stigma and help‐seeking. Mistrust of Western healthcare system describes the participants concerns about the cultural disconnect between the community and the Western healthcare system. Finally, denial of mental illness reflected the community views on mental health. This study provides an insight into the factors that influence the Somali‐Australian community help‐seeking with mental health services. The findings have implications for mental health professionals and the Somali‐Australian community.
Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control
Authors: Ponirakis Georgios , Abdul‐Ghani Muhammad A , Jayyousi Amin , Zirie Mahmoud A , Qazi Murtaza , Almuhannadi Hamad , Petropoulos Ioannis N , Khan Adnan , Gad Hoda , Migahid Osama , Megahed Ayman , Al‐Mohannadi Salma , AlMarri Fatema , Al‐Khayat Fatima , Mahfoud Ziyad , Al Hamad Hanadi , Ramadan Marwan , DeFronzo Ralph , Malik Rayaz A
Published: March 2021

Aims/Introduction

Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control.

Materials and Methods

This exploratory substudy of an open‐label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants with and without pDPN treated with exenatide and pioglitazone or basal–bolus insulin at baseline and 1‐year follow up, and 18 controls at baseline only.

Results

Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P < 0.0001) and weight gain (P < 0.005), irrespective of therapy. Participants with pDPN showed a significant increase in corneal nerve fiber density (P < 0.05), length (P < 0.0001) and branch density (P < 0.005), and a decrease in the Douleur Neuropathique en 4 score (P < 0.01), but no change in electrochemical skin conductance or vibration perception threshold. Participants without pDPN showed a significant increase in corneal nerve branch density (P < 0.01) and no change in any other neuropathy measures. A change in the severity of painful symptoms was not associated with corneal nerve regeneration and medication for pain.

Conclusions

This study showed that intensive glycemic control is associated with greater corneal nerve regeneration and an improvement in the severity of pain in patients with painful diabetic neuropathy.