bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of different selection policies on subcutaneous ICD implants and therapies
Authors: Harding Idris , Kaura Amit , Yue Arthur , Roberts Paul , Murgatroyd Francis , Scott Paul A
Published: May 2020

Background

Patients with existing or anticipated indications for cardiac resynchronisation therapy (CRT), bradycardia, or anti‐tachycardia pacing should not be offered subcutaneous defibrillators (SQIDs) but it remains unclear how clinicians should predict future need for these therapies.

Methods

We applied three SQID selection policies to data collected retrospectively from transvenous implantable cardioverter defibrillator (TV‐ICD) implants:

(a) approach A, SQID used in inherited channelopathies and idiopathic ventricular fibrillation only;

(b) approach B, as above, plus all hypertrophic cardiomyopathy and grown‐up congenital heart disease patients;

(c) approach C, as above, plus primary and secondary prevention (for ventricular fibrillation only) of SCD in patients with QRS <150 ms. Approach C reflects current ESC and AHA/ACC/HRS guidelines.

Results

338 of 951 patients with TV‐ICD were considered for SQID after excluding 613 patients with contraindications. Approaches A, B, and C yielded 45 (4.7%), 89 (9.4%), and 338 (35.5%) patients suitable for SQID, respectively. Use of SQID resulted in more frequent ICD shocks compared to TV‐ICD with approach C only (0.43 vs 0.23 per 1000 patient‐days; P = .03). Rates of CRT upgrade were comparable across selection criteria (0, 0.03, and 0.07 per 1000 patient‐days for approaches A, B, and C, respectively; P = NS). Risk of early mortality was higher when more liberal inclusion criteria were used (P = .003).

Conclusions

One in three patients receiving ICDs may be suitable for SQID under current ESC and AHA/ACC/HRS guidelines. This proportion is influenced significantly by the selection criteria used, and the criteria used by a physician should be informed by the estimated survival of the patient, risk of shocks for MVT, future pacing, and CRT requirements.
Cycles of Gender Convergence and Divergence in Drug Overdose Mortality
Authors: Ho Jessica Y.
Published: May 2020

The United States is 25 years into a large‐scale drug overdose epidemic, yet its consequences for gender differences remain largely unexplored. This study finds that drug overdose mortality increased seven‐ and fivefold for men and women, respectively; accounts for 0.8‐year (men) and 0.4‐year (women) deficits in life expectancy at birth in 2017; and has made an increasing contribution (from 1 percent to 17 percent) to women's life expectancy advantage at the prime adult ages between 1990 and 2017. I document a distinctive cyclicality to sex differences in drug overdose. During the epidemic's early stages—the heyday of prescription opioids—gender differences narrowed, but once the epidemic transitioned to illicit drugs in 2010, gender differences widened again. This pattern holds across racial/ethnic groups, and in fact may be even stronger among Hispanics and non‐Hispanic blacks than among non‐Hispanic whites. That we observe this gender dynamic across racial/ethnic groups is surprising since very different trends in drug overdose mortality have been observed for whites versus other groups. The contemporary epidemic is a case of dynamic change in gender differences, and the differential mortality risks experienced by men and women reflect gendered social norms, attitudes toward risk, and patterns of diffusion.
Another Gendered Demographic Dividend: Adjusting to a Future without Sons
Authors: Allendorf Keera
Published: May 2020

Sonless families may pose a gendered demographic dividend. As fertility declines, families with only daughters are likely to grow. In turn, patriarchal family systems may weaken when many families are unable to engage in patriarchal practices. I examine some of these theorized dynamics in India. Sonless families did grow as fertility declined, reaching 10 percent in India as a whole in 2015 and approaching 20 percent in states with earlier fertility declines. I also identify a substantial influence of children's sex on mothers’ expectations of old‐age support. Using panel data from the India Human Development Survey, I compare women's expectations after they had children to earlier expectations when they did not yet have children. Women with sons kept or further embraced patriarchal expectations that a son would provide support. Sonless mothers largely gave up patriarchal expectations, turning to daughters or away from children altogether.
Novel three‐way complex rearrangement of TRPM1‐PUM1‐LCK in a case of agminated Spitz nevi arising in a giant congenital hyperpigmented macule
Authors: Goto Keisuke , Pissaloux Daniel , Durand Luc , Tirode Franck , Guillot Bernard , de la Fouchardière Arnaud
Published: May 2020

The genetic anomalies associated with the agminated variant of Spitz nevus have so far been limited to HRAS G13R mutations, especially when arising within a nevus spilus. A previous report exposed the case of a man with a giant pigmented macule involving his upper right limb and trunk. Since childhood, Spitz nevi have been periodically arising, within the pigmented area. The histopathology of several lesions displayed the usual criteria of junctional, compound, or intradermal Spitz nevi with a diversity of cytomorphological and architectural features. Some lesions spontaneously regressed. Genetic studies confirmed in three lesions an identical translocation involving TRPM1, PUM1, and LCK. No mutations in HRAS, NRAS, BRAF, or other known fusion genes linked to Spitz nevus were detected. LCK break‐apart fluorescence in situ hybridization confirmed the rearrangement was present not only in the melanocytic proliferation but also in the surrounding non‐spitzoid melanocytes. This report expands the list of genetic alterations involved both in giant congenital macules and in agminated Spitz nevi, and also extends the concept of mosaicism in melanocytes to gene translocations.
Premature senescence in human melanocytes after exposure to solar UVR: An exosome and UV‐miRNA connection
Authors: Sha Jingfeng , Arbesman Joshua , Harter Marian L.
Published: May 2020

Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in vitro. Repeated doses of UVR induced these melanocytes into a senescent‐like state. Additionally, these cells secrete exosomes with specific miRNAs that differ in quantity from those of the un‐irradiated melanocytes. Many of the exosomal miRNAs that were differentially enriched regulated genes comprising a “senescence core signature” and encoding factors of the senescence‐messaging secretome (SASP), while a subset of the differentially reduced miRNAs targeted DNA repair genes that have been experimentally shown to be repressed in senescent melanocytes. Thus, the selection of specific miRNAs by exosomes and their release from melanocytes after exposure to UVR have activities in inducing these cells into premature senescence.
Chilblains in children in the setting of COVID‐19 pandemic
Authors: Andina David , Noguera‐Morel Lucero , Bascuas‐Arribas Marta , Gaitero‐Tristán Jara , Alonso‐Cadenas José Antonio , Escalada‐Pellitero Silvia , Hernández‐Martín Ángela , de la Torre‐Espi Mercedes , Colmenero Isabel , Torrelo Antonio
Published: May 2020

Background

Different skin manifestations of COVID‐19 are being reported. Acral lesions on the hands and feet, closely resembling chilblains, have been recognized during the peak incidence of the COVID‐19 pandemic.

Material and methods

A retrospective review of 22 children and adolescents with chilblain‐like lesions seen over a short period of time in the Emergency Department of a children's hospital during the peak incidence of COVID‐19 in Madrid, Spain.

Results

All patients had lesions clinically consistent with chilblains of the toes or feet, with three also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited, and only 10 had mild respiratory and/or GI symptoms. None had fever. Coagulation tests, hemogram, serum chemistry, and lupus anticoagulant were normal in all patients tested. One out of 16 tested cases had elevated D‐dimer results, but without systemic symptoms or other laboratory anomalies. SARS‐CoV‐2 PCR tested in 19 cases was positive in just one case. Skin biopsies obtained in six patients were consistent with chilblains. On follow‐up, all cases showed spontaneous marked improvement or complete healing.

Conclusion

Acute chilblains were observed during COVID‐19 pandemic in children and teenagers. It is a mildly symptomatic condition with an excellent prognosis, usually requiring no therapy. Etiopathogenesis remains unknown.
Impacts of physical late effects on presenteeism in childhood cancer survivors
Authors: Soejima Takafumi , Sato Iori , Takita Junko , Koh Katsuyoshi , Kaneko Takashi , Inada Hiroko , Ozono Shuichi , Kamibeppu Kiyoko
Published: May 2020

Background

Many childhood cancer survivors (CCSs) experience physical late effects related to their cancer types and treatment modalities. Physical late effects are an important factor in various occupational outcomes among CCSs. However, the relationship between physical late effects and presenteeism has remained unclear. This study aimed to estimate the impacts of physical late effects on presenteeism among employed CCSs.

Methods

Childhood cancer survivors replied to a questionnaire regarding presenteeism, and their attending physicians assessed their physical late effects between September 2014 and December 2015. The Work Limitations Questionnaire was used to measure presenteeism. Propensity score analysis and a generalized linear model were used to adjust covariates related to physical late effects and / or presenteeism.

Results

Of the 125 questionnaires distributed, 114 were returned. The data from 61 employed CCSs were analyzed. After controlling for covariates by propensity score analysis and generalized linear model, there were no significant differences in presenteeism between employed CCSs with either no or single physical late effects. However, employed CCSs with multiple physical late effects reported higher scores in Output (Estimate = 9.3,P= 0.041), Physical Demands (Estimate = 12.2,P= 0.020), and Productivity Loss scores (Estimate = 2.4,P= 0.045) on the Work Limitations Questionnaire than employed CCSs with no physical late effects.

Conclusions

Employed CCSs with multiple physical late effects were at an increased risk for presenteeism. Healthcare and social welfare systems should be established to provide vocational assistance for CCSs after being employed to alleviate presenteeism.
What drives interspecies graft union success? Exploring the role of phylogenetic relatedness and stem anatomy
Authors: Wulf Kate E. , Reid James B. , Foo Eloise
Published: May 2020

The underlying mechanisms that determine whether two species can form a successful graft union (graft compatibility) remain obscure. Two prominent hypotheses are (1) the more closely related species are, the higher the graft success and (2) the vascular anatomy at the graft junction influences graft success. In this paper these two hypotheses are examined in a systematic way using graft combinations selected from a range of (a) phylogenetically close and more distant legume species, (b) species displaying different germination patterns and (c) scions and rootstocks possessing contrasting stem tissues and vascular patterns. Relatedness of species was not a good predictor of graft compatibility, as vascular reconnection can occur between distantly related species and can fail to occur in some more closely related species. Similarly, neither the stem tissues present at the graft junction nor the vascular anatomy correlated with the success of vascular reconnection. Relatedness and stem anatomy therefore do not appear to be the determining factors in successful vascular reconnection after grafting in legumes. These results are discussed in conjunction with other hypotheses such as the role of auxin.
Effects of periodontal disease on glycemic control, complications, and incidence of diabetes mellitus
Authors: Genco Robert J. , Graziani Filippo , Hasturk Hatice
Published: May 2020

Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged ≥65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications.
Periodontal disease and adverse pregnancy outcomes
Authors: Bobetsis Yiorgos A. , Graziani Filippo , Gürsoy Mervi , Madianos Phoebus N.
Published: May 2020

Periodontal diseases are considered not only to affect tooth‐supporting tissues but also to have a cause‐and‐effect relationship with various systemic diseases and conditions, such as adverse pregnancy outcomes. Mechanistic studies provide strong evidence that periodontal pathogens can translocate from infected periodontium to the feto‐placental unit and initiate a metastatic infection. However, the extent and mechanisms by which metastatic inflammation and injury contribute to adverse pregnancy outcomes still remain unclear. The presence of oral bacteria in the placenta of women with term gestation further complicates our understanding of the biology behind the role of periodontal pathogens in pregnancy outcomes. Epidemiological studies demonstrate many methodological inconsistencies and flaws that render comparisons difficult and conclusions insecure. Therefore, despite the fact that a number of prospective studies show a positive association between periodontal diseases and various adverse pregnancy outcomes, the evidence behind it is still weak. Future well‐designed explanatory studies are necessary to verify this relationship and, if present, determine its magnitude. The majority of high‐quality randomized controlled trials reveal that nonsurgical periodontal therapy during the second trimester of gestation does not improve pregnancy outcomes. From a biological standpoint, this can be partially explained by the fact that therapy rendered at the fourth to sixth months of pregnancy is too late to prevent placental colonization by periodontal pathogens and consequently incapable of affecting pathogen‐induced injury at the feto‐placental unit. Thus, interventions during the preconception period may be more meaningful. With the increase in our understanding on the potential association between periodontal disease and adverse pregnancy outcomes, it is clear that dental practitioners should provide periodontal treatment to pregnant women that is safe for both the mother and the unborn child. Although there is not enough evidence that the anti‐infective therapy alters pregnancy outcomes, it improves health‐promoting behavior and periodontal condition, which in turn advance general health and risk factor control.
The role of the microbiota in periodontal disease
Authors: Curtis Mike A. , Diaz Patricia I. , Van Dyke Thomas E.
Published: May 2020

The last decade has witnessed unparalleled advances in our understanding of the complexity of the oral microbiome and the compositional changes that occur in subgingival biofilms in the transition from health to gingivitis and to destructive periodontal disease. The traditional view, which has held sway for the last 2 decades, that disease is characterized by the outgrowth of a consortium, or consortia, of a limited number of potentially pathogenic organisms, has given way to an alternative paradigm. In this new view, the microbiological changes associated with disease represent whole‐scale alterations to the overall microbial population structure and to the functional properties of the entire community. Thus, and in common with other microbially mediated diseases of the gastrointestinal tract, the normally balanced, symbiotic, and generally benign commensal microbiome of the tooth‐associated biofilm undergoes dysbiosis to a potentially deleterious microbiota. Coincident with progress in defining the microbiology of these diseases, there have been equally important advances in our understanding of the inflammatory systems of the periodontal tissues, their control, and how inflammation may contribute both to the development of dysbiosis and, in a deregulated state, the destructive disease process. One can therefore speculate that the inflammatory response and the periodontal microbiome are in a bidirectional balance in oral health and a bidirectional imbalance in periodontitis. However, despite these clear insights into both sides of the host/microbe balance in periodontal disease, there remain several unresolved issues concerning the role of the microbiota in disease. These include, but are not limited to, the factors which determine progression from gingivitis to periodontitis in a proportion of the population, whether dysbiosis causes disease or results from disease, and the molecular details of the microbial stimulus responsible for driving the destructive inflammatory response. Further progress in resolving these issues may provide significant benefit to diagnosis, treatment, and prevention.
Diabetes as a risk factor for periodontal disease—plausible mechanisms
Authors: Polak David , Sanui Terukazu , Nishimura Fusanori , Shapira Lior
Published: May 2020

The present narrative review examines the scientific evidence of the biological mechanisms that may link periodontitis and diabetes, as a source of comorbidity. Publications regarding periodontitis and diabetes, in human, animals, and in vitro were screened for their relevance. Periodontal microbiome studies indicate a possible association between altered glucose metabolism in prediabetes and diabetes and changes in the periodontal microbiome. Coinciding with this, hyperglycemia enhances expression of pathogen receptors, which enhance host response to the dysbiotic microbiome. Hyperglycemia also promotes pro‐inflammatory response independently or via the advanced glycation end product/receptor for advanced glycation end product pathway. These processes excite cellular tissue destruction functions, which further enhance pro‐inflammatory cytokines expression and alteration in the RANKL/osteoprotegerin ratio, promoting formation and activation of osteoclasts. The evidence supports the role of several pathogenic mechanisms in the path of true causal comorbidity between poorly controlled diabetes and periodontitis. However, further research is needed to better understand these mechanisms and to explore other mechanisms.
Periodontal therapy and cardiovascular risk
Authors: Orlandi Marco , Graziani Filippo , D'Aiuto Francesco
Published: May 2020

Cardiovascular diseases are the worldwide leading cause of mortality. Cardiovascular diseases are noncommunicable conditions with a complex pathogenesis, and their clinical manifestations include major cardiovascular events such as myocardial infarction and stroke. Epidemiologic evidence suggests a consistent association between periodontitis and increased risk of cardiovascular diseases. Some evidence supports a beneficial effect of the treatment of periodontitis on both surrogate and hard cardiovascular outcomes. This narrative review has been conducted as an update of the most recent evidence on the effects of periodontitis treatment on cardiovascular outcomes since the last commissioned review of the European Federation of Periodontology‐American Academy of Periodontology World Workshop in 2012. Newer evidence originating from published randomized controlled trials confirms a positive effect of periodontal treatment on surrogate measures of cardiovascular diseases, whereas there have been no randomized controlled trials investigating the effect of periodontal treatment on the incidence of cardiovascular disease events such as myocardial infarction and stroke. In conclusion, there is sufficient evidence from observational and experimental studies on surrogate cardiovascular measures to justify the design and conduct of appropriately powered randomized controlled trials investigating the effect of effective periodontal interventions on cardiovascular disease outcomes (ie, myocardial infarction and stroke) with adequate control of traditional cardiovascular risk factors.
Patient‐based outcomes and quality of life
Authors: Graziani Filippo , Tsakos Georgios
Published: May 2020

Patient‐based outcomes complement clinical data with patients’ self‐evaluation of their physical, psychological, and social well‐being, and as such facilitate clinical decision‐making, assessing the quality of care provided, and evaluating practices and policies. Some validated generic oral health‐related quality of life measures used in recent research indicated a high performance. There is a proportional relationship between the quality of life and periodontitis, ie, the higher the level of periodontitis, the poorer the oral health‐related quality of life. This relationship is heightened by the presence of symptoms such as bleeding, halitosis, and mobility. On the other hand, periodontal treatment has demonstrated the capability to improve quality of life substantially. Future research should focus on questionnaires that are able to explain the interlinked pathways between periodontal conditions, approaches to treatment approaches, and patients’ well‐being. The acquisition of new knowledge in the field is essential for the whole community, as we treat people not millimeters.
Primer on etiology and treatment of progressive/severe periodontitis: A systemic health perspective
Authors: Slots Jørgen
Published: May 2020

Periodontology is an infectious disease‐based discipline. The etiopathology of progressive/severe periodontitis includes active herpesviruses, specific bacterial pathogens, and proinflammatory cytokines. Herpesviruses and periodontopathic bacteria may interact synergistically to produce periodontal breakdown, and periodontal herpesviruses may contribute to systemic diseases. The infectious agents of severe periodontitis reside in deep pockets, furcation lesions, and inflamed gingiva, sites inaccessible by conventional (purely mechanical) surgical or nonsurgical therapy but accessible by systemic antibiotic treatment. This brief overview presents an effective anti‐infective treatment of severe periodontitis, which includes systemic chemotherapy/antibiotics against herpesviruses (valacyclovir [acyclovir]) and bacterial pathogens (amoxicillin + metronidazole or ciprofloxacin + metronidazole) plus common antiseptics (povidone‐iodine and sodium hypochlorite) and select ultrasonic scaling. The proposed treatment can cause a marked reduction or elimination of major periodontal pathogens, is acceptably safe, and can be carried out in minimal time with minimal cost.
The association of periodontal diseases with metabolic syndrome and obesity
Authors: Jepsen Søren , Suvan Jean , Deschner James
Published: May 2020

Periodontitis is a multifactorial chronic inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth‐supporting apparatus. Globally, it is estimated that 740 million people are affected by its severe form. Periodontitis has been suggested to be linked to obesity and metabolic syndrome. Obesity, defined as excessive fat accumulation, is a complex multifactorial chronic inflammatory disease, with a high and increasing prevalence. Metabolic syndrome is defined as a cluster of obesity, dyslipidemia, hypertension, and dysglycemia. Obesity, metabolic syndrome and periodontitis are among the most common non‐communicable diseases and a large body of evidence from epidemiologic studies supports the association between these conditions. Extensive research has established plausible mechanisms to explain how these conditions can negatively impact each other, pointing to a bidirectional adverse relationship. At present there is only limited evidence available from a few intervention studies. Nevertheless, the global burden of periodontitis combined with the obesity epidemic has important clinical and public health implications for the dental team. In accordance with the common risk factor approach for tackling non‐communicable diseases, it has been proposed that oral healthcare professionals have an important role in the promotion of periodontal health and general well‐being through facilitation of healthy lifestyle behaviours.
Periodontal disease as a possible cause for Alzheimer's disease
Authors: Kamer Angela R. , Craig Ronald G. , Niederman Richard , Fortea Juan , de Leon Mony J.
Published: May 2020

Approximately 47 million people worldwide have been diagnosed with dementia, 60%‐80% of whom have dementia of the Alzheimer’s disease type. Unfortunately, there is no cure in sight. Defining modifiable risk factors for Alzheimer’s disease may have a significant impact on its prevalence. An increasing body of evidence suggests that chronic inflammation and microbial dysbiosis are risk factors for Alzheimer’s disease. Periodontal disease is a chronic inflammatory disease that develops in response to response to microbial dysbiosis. Many studies have shown an association between periodontal disease and Alzheimer’s disease. The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer’s disease.
Periodontal disease and cancer: Epidemiologic studies and possible mechanisms
Authors: Nwizu Ngozi , Wactawski‐Wende Jean , Genco Robert J.
Published: May 2020

Epidemiologic and cancer control studies on the association of periodontal disease and cancer risk mostly suggest a positive association with overall cancer risk and certain specific types of cancer. These findings are generally consistent among cross‐sectional and longitudinal studies. In this paper, we review epidemiologic studies and current knowledge on periodontal disease and cancer, with a focus on those studies conducted in the years following the Joint European Federation of Periodontology/American Academy of Periodontology Workshop on “Periodontitis and Systemic Diseases” in November 2012. This review also explores the role of chronic inflammation as a biologically plausible mechanistic link between periodontal disease and risk of cancer. Furthermore, it highlights studies that have examined the potential importance of certain periodontal pathogens in this association.
Clinical and public health implications of periodontal and systemic diseases: An overview
Authors: Genco Robert J. , Sanz Mariano
Published: May 2020

Severe periodontitis is defined by extensive loss of the tooth attachment apparatus. It is the sixth most common human disease and is estimated to affect 11.2% of the global adult population, hence representing a significant healthcare, social, and economic burden. Since the 1990s, multiple epidemiologic, experimental, and interventional studies have evidenced how periodontitis may also impact systemic health and it has been independently associated with the majority of chronic noncommunicable diseases. The evidence supporting these associations, mainly focusing on diabetes, pregnancy complications, and cardiovascular disease, was thoroughly reviewed in 2012 by an international consensus workshop. In the last 5 years, however, important advances have been made, not only in our understanding of the etiopathogenesis of periodontitis, or concerning the mounting evidence regarding the independent associations between periodontitis, diabetes, and cardiovascular disease, but also with many other systemic diseases including metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders including Alzheimer's disease. This review describes these scientific advances by gathering together the existing evidence on the importance and relevance of the associations between periodontitis and many systemic diseases.
Testing Relevant Hypotheses in Functional Time Series via Self-Normalization
Authors: Dette Holger , Kokot Kevin , Volgushev Stanislav
Published: May 2020

We develop methodology for testing relevant hypotheses about functional time series in a tuning-free way. Instead of testing for exact equality, e.g. for the equality of two mean functions from two independent time series, we propose to test the null hypothesis of no relevant deviation. In the two-sample problem this means that an L2-distance between the two mean functions is smaller than a prespecified threshold. For such hypotheses self-normalization, which was introduced in 2010 by Shao, and Shao and Zhang and is commonly used to avoid the estimation of nuisance parameters, is not directly applicable. We develop new self-normalized procedures for testing relevant hypotheses in the one-sample, two-sample and change point problem and investigate their asymptotic properties. Finite sample properties of the tests proposed are illustrated by means of a simulation study and data examples. Our main focus is on functional time series, but extensions to other settings are also briefly discussed.
The relationships of job and family demands and job and family resources with family caregivers’ strain
Authors: Boumans Nicolle P. G. , Dorant Elisabeth
Published: May 2020

Background

Because of an expected increase in the number of family caregivers, there is a growing public and scientific interest in family caregiving and more specifically in the combination of family care with paid employment. It is important to gain insight in the family caregivers’ strain and determining factors in the job and family domain.

Aim

The aim of the study was to examine the associations of job and family demands and job and family resources with indicators of caregivers’ psychological strain, that is caregiver burden, work‐related emotional exhaustion and general ill mental health. In our research, we focused on individuals who combine paid employment with family caregiving.

Methods

A cross‐sectional design was used. The study sample was derived in 2011 from a Dutch financial organisation and a healthcare organisation. A digital fully structured questionnaire was used. The sample consisted of 187 employees who identified themselves as family caregivers. Descriptive statistics and hierarchical linear regression analysis were performed.

Results

Job demands (i.e. workload, work–family conflict) and family demands (i.e. family care hours and family–work conflict) were significantly positively associated with all three domain‐specific indicators of strain. The resources of work–family and family–work enrichment and autonomy did not contribute to less experienced strain. More supervisor and colleague support was associated with lower ill mental health.

Conclusion

Our study showed that job demands (workload, work–family conflict) and family demands (family care hours, family–work conflict) were clearly associated with caregiver strain, while associations for job and family resources were not evident. It remains necessary to pay attention to the demanding aspects of dual roles of family caregivers but also to investigate the resources they have available at work as well as in their home situation and explore their potential reducing effect on family caregivers’ strain.
Aragonite depositional facies in a Late Ordovician calcite sea, Eastern Laurentia
Authors: James Noel P. , Narbonne Guy M. , Armstrong Alexis K. R.
Published: May 2020

The Black River (Upper Ordovician – Sandbian) and Trenton (Upper Ordovician – Katian) groups are traditionally interpreted as a deepening‐upward succession deposited in a progressively subsiding Appalachian Basin margin that contained warm‐water, marine, photozoan deposits that pass upward into cool‐water, marine, heterozoan carbonates. This succession is customarily interpreted to reflect an incursion of cold, high‐latitude ocean waters into the area. This view is herein confirmed for coeval carbonates in the northern part of the basin, particularly the St. Lawrence Platform. They are now well explained in this study on the basis of recent studies of cool‐water carbonates and calcite–aragonite seas. Overall the succession is one of Sandbian photozoan ramp deposits succeeded by Katian heterozoan ramp carbonates that changed back to photozoan ramp deposits prior to the Hirnantian glaciation. The current interpretation, that deposition took place throughout a calcite sea time, seems at odds with this series of strata. Instead it is herein proposed that deposition took place during an aragonite sea time wherein calcite sea‐like sediments accumulated under cold ocean‐water temperatures. Such an interpretation is supported by recent experimental data that supports the importance of seawater temperature on CaCO3 polymorph precipitation. If correct, this means that some of the evidence for calcite sea deposition through time brought about by global tectonics, should be re‐evaluated to make sure it was not simply cool‐water carbonate production.
We have our dignity, yeah? Scrutiny under suspicion: Experiences of welfare conditionality in the Irish social protection system
Authors: Whelan Joe
Published: May 2020

Conditionality has arguably always been part of welfare and poor relief regimes dating at least as far back as the poor laws and the condition of less eligibility. Nevertheless, there has arguably been a more pronounced turn towards welfare conditionality in the latter part of the 20th and beginning of the 21st centuries and this appears to be continuing across jurisdictions largely unabated and despite the fact that large amounts of evidence continue to suggest the ineffectiveness of welfare conditionality as means of promoting re‐ entry to the workforce for those experiencing unemployment. Alongside this, much evidence also points to the ultimately deleterious effects of welfare conditionality on those at whom it is targeted. This is an area which has seen an abundance of recent contributions in the context of the UK and further afield but that has arguably suffered from a lack of cognate data that sheds light on the Irish example. In attempting to begin to remedy this, this article presents data from a series of interviews carried out with welfare recipients in Ireland in 2018. The purpose of this article is to shed light on experiences of conditionality in the contemporary Irish welfare state and to attempt to nuance further what conditionality can mean. In doing so, this article takes the approach of allowing the data to “speak for itself” in order to best showcase the experiences of those most affected by welfare conditionality.
Prediction of cytomegalovirus infection: A single‐center experience utilizing a newly available cell‐mediated immunity assay by flow cytometry, a risk factor screening tool, and serologically demonstrated immunity
Authors: Jorgenson Margaret R. , Hillis Mikala I. , Saddler Christopher M. , Smith Jeannina A. , Parajuli Sandesh , Mandelbrot Didier A.
Published: May 2020

Purpose

Describe use and predictive potential of an intracellular cytokine staining (ICS) cytomegalovirus cell‐mediated immunity (CMV CMI) assay and a risk factor screening tool on CMV reactivation in a real‐world clinical setting and compare this to serologically demonstrated immunity by CMV IGG.

Methods

Adult transplant patients at our center with the ICS assay resulted between 10/1/2018 and 9/1/2019 were included. Assays were considered positive per manufacturer specifications.

Results

Twenty‐five patients underwent ICS CMV CMI testing at our institution during the study period. The majority were kidney transplant recipients, 76% were D+/R−, and 76% were receiving CMV treatment. The positive predictive value (PPV) of the assay to predict lack of CMV was 87%; 93% when patients with antiviral resistance were excluded and 91% in only those receiving treatment. The presence of ≤2 clinical risk factors on the screening tool had a PPV of 92% in predicting lack of recurrence. In comparison, serologically demonstrated immunity by CMV IGG had a PPV of 62%.

Conclusions

In our study representing real‐world clinical use, the ICS CMV CMI assay and the risk factor screening tool had predictive potential that was superior to serologically demonstrated immunity. The reliability of the assay seemed to decrease with higher degrees of clinical risk suggesting a multimodal screening approach is warranted.
Polymyxin B‐induced skin hyperpigmentation
Authors: Li Yumeng M. , Milikowski Clara , Selvaggi Gennaro , Abbo Lillian M. , Skiada Dimitra , Galimberti Fabrizio
Published: May 2020

Polymyxin B (PMB) is a potent antibiotic targeting gram‐negative bacteria and is associated with serious side effects including nephrotoxicity, neurotoxicity, and hypersensitivity reactions. PMB is a therapeutic option for the management of infections caused by multi‐drug‐resistant (MDR) bacteria and used in combination with other antibiotics when options are limited. We describe the case of a 30‐year‐old female patient with a complex medical history who underwent a multi‐visceral transplantation complicated by intra‐abdominal infections. Subsequently, patient developed diffuse skin darkening after initiation of intravenous PMB for treatment of MDR Pseudomonas aeruginosa. Her skin hyperpigmentation was most prominent on her face and forearms. Hyperpigmentation peaked at around 2 weeks following PMB initiation and was discontinued after 3 weeks when the possibility of PMB hyperpigmentation was raised and other causes were ruled out. Skin biopsy showed hypermelanosis of the basal layer and melanin deposition in the dermis. Overall clinical picture was consistent with PMB‐induced hyperpigmentation. The patient demonstrated some improvement in discoloration within 4 weeks of PMB discontinuation.
Mycobacterium haemophilum skin and soft tissue infection in a kidney transplant recipient: A case report and summary of the literature
Authors: Jurairattanaporn Natthachat , Vachiramon Vasanop , Bruminhent Jackrapong
Published: May 2020

Non‐tuberculous mycobacteria are ubiquitous pathogens causing infections in immunocompromised patients. Here, we describe a kidney transplant recipient who developed skin and soft tissue infection by Mycobacterium haemophilum, complicated by tenosynovitis and fluid collection, following an injury sustained to her right foot. Her immunosuppressant dose was reduced, and she underwent prolonged antimicrobial therapy followed by surgical debridement with a favorable outcome. Non‐tuberculous mycobacteria should be considered as a potential etiology of subacute skin and soft tissue infections.
Persistent BK polyomavirus‐DNAemia may warrant cystoscopy to rule out urologic carcinoma: A case report and review of the literature
Authors: Prom Alyson , Jorgenson Margaret , Alagusundaramoorthy Sayee , Parajuli Sandesh
Published: May 2020

There is minimal literature describing the clinical workup of patients with persistent BKPyV‐DNAemia despite aggressive immunosuppressive reduction. We present a case herein of persistent BKPyV‐DNAemia with significant discordance of BK viruria level in a kidney transplant recipient found to have bladder carcinoma. Based on our findings, we recommend evaluating the urine of patients with persistent BKPyV‐DNAemia for BK viruria. If there is significant discordance in the level of BKPyV‐DNAemia and viruria, cystoscopy should be pursued to rule out bladder or uroepithelial malignancies.
Macrolide‐resistant Mycoplasma pneumoniae pneumonia in transplantation: Increasingly typical?
Authors: Eschenauer Gregory A. , Xiao Li , Waites Ken B. , Crabb Donna M. , Ratliff Amy E. , Gandhi Tejal N. , Riddell James , Kaul Daniel R
Published: May 2020

Mycoplasma pneumoniae is one of the most common bacterial causes of pneumonia. Macrolide‐resistant M pneumoniae (MRMP) was documented in 7.5% of isolates in the United States. Resistance portends poor outcomes to macrolide therapy, yet patients respond well to fluoroquinolones or tetracyclines such as minocycline. However, MRMP may be under‐appreciated because M pneumoniae generally causes relatively mild infections in non‐immunosuppressed adults that may resolve without effective therapy and because microbiological confirmation and susceptibility are not routinely performed. We report two cases of pneumonia due to MRMP in kidney transplant recipients. Both patients required hospital admission, worsened on macrolide therapy, and rapidly defervesced on doxycycline or levofloxacin. In one case, M pneumoniae was only identified by multiplex respiratory pathogen panel analysis of BAL fluid. Macrolide resistance was confirmed in both cases by real‐time PCR and point mutations associated with macrolide resistance were identified. M pneumoniae was isolated from both cases, and molecular genotyping revealed the same genotype. In conclusion, clinicians should be aware of the potential for macrolide resistance in M pneumoniae, and may consider non‐macrolide‐based therapy for confirmed or non‐responding infections in patients who are immunocompromised or hospitalized.
Ethyl glucuronide, a marker of alcohol consumption, correlates with metabolic markers of oxidant stress but not with hemolysis in stored red blood cells from healthy blood donors
Authors: D'Alessandro Angelo , Fu Xiaoyun , Reisz Julie A. , Stone Mars , Kleinman Steve , Zimring James C. , Busch Michael ,   for the Recipient Epidemiology and Donor Evaluation Study‐III (REDS III)
Published: May 2020

BACKGROUND

Red blood cell (RBC) storage in the blood bank is associated with the progressive accumulation of oxidant stress. While the mature erythrocyte is well equipped to cope with such stress, recreative habits like alcohol consumption may further exacerbate the basal level of oxidant stress and contribute to the progress of the storage lesion.

STUDY DESIGN AND METHODS

RBC levels of ethyl glucuronide, a marker of alcohol consumption, were measured via ultra‐high‐pressure liquid chromatography coupled with high‐resolution mass spectrometry. Analyses were performed on 599 samples from the recalled donor population at Storage Days 10, 23, and 42 (n = 250), as part of the REDS‐III RBC‐Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell‐Omics) study. This cohort consisted of the 5th and 95th percentile of donors with extreme hemolytic propensity out of the original cohort of 13,403 subjects enrolled in the REDS‐III RBC Omics study. Ehtyl glucuronide levels were thus correlated to global metabolomics and lipidomics analyses and RBC hemolytic propensity.

RESULTS

Ethyl glucuronide levels were positively associated with oxidant stress markers, including glutathione consumption and turnover, methionine oxidation, S‐adenosylhomocysteine accumulation, purine oxidation, and transamination markers. Decreases in glycolysis and energy metabolism, the pentose phosphate pathway and ascorbate system were observed in those subjects with the highest levels of ethyl glucuronide, though hemolysis values were comparable between groups.

CONCLUSION

Though preliminary, this study is suggestive that markers of alcohol consumption are associated with increases in oxidant stress and decreases in energy metabolism with no significant impact on hemolytic parameters in stored RBCs from healthy donor volunteers.
Developments and translational relevance for the canine haematopoietic cell transplantation preclinical model
Authors: Graves Scott S. , Storb Rainer
Published: May 2020

The development of safe and reliable haematopoietic cell transplantation (HCT) protocols to treat human patients with malignant and non‐malignant blood disorders was highly influenced by preclinical studies obtained in random‐bred canines. The surmounted barriers included recognizing the crucial importance of histocompatibility matching, establishing long‐term donor haematopoietic cell engraftment, preventing graft‐vs‐host disease and advancing effective conditioning and post‐grafting immunosuppression protocols, all of which were evaluated in canines. Recent studies have applied the tolerance inducing potential of HCT to solid organ and vascularized composite tissue transplantation. Several advances in HCT and tolerance induction that were first developed in the canine preclinical model and subsequently applied to human patients are now being recruited into veterinary practice for the treatment of malignant and non‐malignant disorders in companion dogs. Here, we review recent HCT advancements attained in the canine model during the past 15 years.
Efficacy of adjunctive therapy using Vizoovet in improving clinical signs of keratoconjunctivitis sicca in dogs: A pilot study
Authors: Dees D. Dustin , Kent Michael S.
Published: May 2020

Objective

To assess the clinical safety and efficacy of adjunctive therapy using Vizoovet to ameliorate clinical signs of keratoconjunctivitis sicca (KCS) in dogs.

Animals studied

Twenty client‐owned dogs.

Procedures

Canine patients diagnosed with KCS were enrolled in this prospective study. Patients were randomly selected to receive either Vizoovet or GenTeal drops twice daily in addition to twice daily tacrolimus 0.03% solution. Data were collected from only one eye of each patient and included STT‐1, IOP, TFBUT, and results of objective clinical scoring performed by pet owners. Statistical significance was set atP ≤ .05.

Results

In all, 20 dogs (20 eyes) were enrolled in this prospective randomized study. Females (n = 12; 60%) outnumbered males (n = 8; 40%) and all dogs were spayed/neutered. Mean age of all dogs was 10.6 ± 3.79 years. In both treatment groups, the improvement in STT‐1 values over the course of the study was significant (P = .002). When comparing the STT‐1 improvements between groups, no significance was found (P = .78). In both groups, the improvement in TFBUT was significant (P = .0018). When comparing the TFBUT improvements between groups, no significance was found (P = .14). Squinting, rubbing, ocular discharge, and medication administration scores all significantly improved throughout the course of the study; however, they did not differ significantly between groups. Throughout the study, no adverse side effects were noted clinically or by the pet owner in either group.

Conclusions and Clinical Relevance

Adjunctive treatment with Vizoovet was as safe and effective as GenTeal drops at improving clinical signs of dry eye in dogs.