bluuebunny/crossref_metadata_2025 huggingface dataset:
Red cell distribution width/albumin ratio and 90-day mortality after burn surgery
Authors: Seo Young Joo , Yu Jihion , Park Jun-Young , Lee Narea , Lee Jiwoong , Park Ji Hyun , Kim Hee Yeong , Kong Yu-Gyeong , Kim Young-Kug
Published: December 2021

Background

Red cell distribution width (RDW) and serum albumin concentration are associated with postoperative outcomes. However, the usefulness of the RDW/albumin ratio in burn surgery remains unclear. Therefore, we evaluated the association between RDW/albumin ratio and 90-day mortality after burn surgery.

Methods

Between 2013 and 2020, a retrospective review of patients in a burn intensive care unit (ICU) was performed. Receiver operating characteristic curve, multivariate Cox logistic regression, multivariate logistic regression and Kaplan–Meier analyses were conducted to evaluate the association between RDW/albumin ratio and 90-day mortality after burn surgery. Additionally, prolonged ICU stay rate (>60 days) and ICU stay were assessed.

Results

Ninety-day mortality was 22.5% (210/934) in burn patients. Risk factors for 90-day mortality were RDW/albumin ratio at postoperative day 1, age, American Society of Anesthesiologists physical status, diabetes mellitus, inhalation injury, total body surface area burned, hypotensive event and red blood cell transfusion volume. The area under the curve of the RDW/albumin ratio at postoperative day 1 to predict 90-day mortality, after adjusting for age and total body surface area burned, was 0.875 (cut-off value, 6.8). The 90-day mortality was significantly higher in patients with RDW/albumin ratio >6.8 than in those with RDW/albumin ratio ≤6.8 (49.2% vs 12.3%, p < 0.001). Prolonged ICU stay rate and ICU stay were significantly higher and longer in patients with RDW/albumin ratio >6.8 than in those with RDW/albumin ratio ≤6.8 (34.5% vs 26.5%; 21 [11–38] vs 18 [7–32] days).

Conclusion

RDW/albumin ratio >6.8 on postoperative day 1 was associated with higher 90-day mortality, higher prolonged ICU stay rate and longer ICU stay after burn surgery.
Investigating the global prevalence and consequences of undiagnosed stage 3 chronic kidney disease: methods and rationale for the REVEAL-CKD study
Authors: Kushner Pamela , Peach Emily , Wittbrodt Eric , Barone Salvatore , Chen Hungta , Sanchez Juan Jose Garcia , Järbrink Krister , Arnold Matthew , Tangri Navdeep
Published: December 2021

Background

Timely diagnosis and treatment of stage 3 chronic kidney disease (CKD) can prevent further loss of kidney function and progression to kidney failure. However, contemporary data on the global prevalence of undiagnosed stage 3 CKD are scarce. REVEAL-CKD is a multinational, multifocal and observational study aiming to provide insights into undiagnosed stage 3 CKD in a large population.

Methods

Patients (aged ≥18 years) with data in selected secondary databases from 11 countries will be included if they have at least two estimated glomerular filtration rate (eGFR) measurements from 2015 onwards that are ≥30 and <60 mL/min/1.73 m2, recorded >90 and ≤730 days apart. Undiagnosed cases are those without an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before and up to 6 months after the second qualifying eGFR measurement. Time to diagnosis will be assessed using a Kaplan–Meier approach; patient characteristics associated with undiagnosed CKD will be assessed using adjusted logistical regression analyses.

Results

REVEAL-CKD will assess the point prevalence of undiagnosed stage 3 CKD and time to CKD diagnosis in initially undiagnosed cases overall and in individual countries. Trends in undiagnosed CKD prevalence by calendar year will be assessed. Patient characteristics, healthcare resource utilization, adverse clinical outcomes, and CKD management and monitoring practices in patients with versus without a CKD diagnosis will be compared.

Conclusions

REVEAL-CKD will increase awareness of the global clinical and economic burden of undiagnosed stage 3 CKD and provide valuable insights to inform clinical practice and policy changes.
Increased 1-year mortality in haemodialysis patients with COVID-19: a prospective, observational study
Authors: Carriazo Sol , Mas-Fontao Sebastian , Seghers Clara , Cano Jaime , Goma Elena , Avello Alejandro , Ortiz Alberto , Gonzalez-Parra Emilio
Published: December 2021

Background

Dialysis confers the highest risk of coronavirus disease 2019 (COVID-19) death among comorbidities predisposing to severe COVID-19. However, reports of COVID-19-associated mortality frequently refer to mortality during the initial hospitalization or first month after diagnosis.

Methods

In a prospective, observational study, we analysed the long-term (1-year follow-up) serological and clinical outcomes of 56 haemodialysis (HD) patients who were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first pandemic wave. COVID-19 was diagnosed by a positive polymerase chain reaction (PCR) test (n = 37) or by the development of anti-SARS-CoV-2 antibodies (n = 19).

Results

After >1 year of follow-up, 35.7% of HD patients infected by SARS-CoV-2 during the first pandemic wave had died, 6 (11%) during the initial admission and 14 (25%) in the following months, mainly within the first 3 months after diagnosis. Overall, 30% of patients died from vascular causes and 40% from respiratory causes. In adjusted analysis, a positive SARS-CoV-2 PCR test for diagnosis {hazard ratio [HR] 5.18 [interquartile range (IQR) 1.30–20.65], P = 0.020}, higher baseline C-reactive protein levels [HR 1.10 (IQR 1.03–1.16), P = 0.002] and lower haemoglobin levels [HR 0.62 (IQR 0.45–0.86), P = 0.005] were associated with higher 1-year mortality. Mortality in the 144 patients who did not have COVID-19 was 21 (14.6%) over 12 months [HR of death for COVID-19 patients 3.00 (IQR 1.62–5.53), log-rank P = 0.00023]. Over the first year, the percentage of patients having anti-SARS-CoV-2 immunoglobulin G (IgG) decreased from 36/49 (73.4%) initially to 27/44 (61.3%) at 6 months and 14/36 (38.8%) at 12 months.

Conclusions

The high mortality of HD patients with COVID-19 is not limited to the initial hospitalization. Defining COVID-19 deaths as those occurring within 3 months of a COVID-19 diagnosis may better represent the burden of COVID-19. In HD patients, the anti-SARS-CoV-2 IgG response was suboptimal and short-lived.
Ethical challenges in managing unvaccinated patients receiving chronic in-centre haemodialysis
Authors: Alfano Gaetano , Fontana Francesco , Morisi Niccolò , Mori Giacomo , Cappelli Gianni , Magistroni Riccardo , Donati Gabriele
Published: December 2021

Insufficient vaccine coverage and dominance of the more transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are the leading causes of the continued spread of coronavirus disease 2019 (COVID-19) worldwide. To curb the surge in infections, COVID-19 vaccination has been advocated as a priority measure, especially for frail populations and people at high risk of exposure. Patients on in-centre maintenance haemodialysis (HD) embody both conditions. They are at high risk of severe COVID-19 consequences due to their advanced age and weakened immune system and carry an increased risk of SARS-CoV-2 transmission within shared dialysis rooms and public vehicles. Vaccination of the entire HD population is therefore the most effective strategy to protect patients from the dire consequences of COVID-19. Unfortunately, a minority of patients still express COVID-19 vaccine hesitancy. The management of this group of patients, who have the full right to HD treatment, poses demanding problems from a patient safety perspective. The placement of unvaccinated patients within the dialysis room and the protection of all vaccinated patients are some of the most urgent problems the nephrologist faces during the COVID-19 pandemic. In light of these COVID-19-driven changes, an ethical reflection on the management of unvaccinated patients appears crucial to act responsibly and contribute to the health promotion of dialysis patients.
Time-updated anion gap and cardiovascular events in advanced chronic kidney disease: a cohort study
Authors: Asahina Yuta , Sakaguchi Yusuke , Kajimoto Sachio , Hattori Koki , Doi Yohei , Oka Tatsufumi , Kaimori Jun-Ya , Isaka Yoshitaka
Published: December 2021

Background

Studies examining associations between metabolic acidosis and cardiovascular events in chronic kidney disease (CKD) have shown conflicting results and have not differentiated between normal anion gap (hyperchloremic) acidosis and high anion gap acidosis. We aimed to examine the impact of normal and high anion gap acidosis, separately, on the risk of cardiovascular events among patients with CKD.

Methods

This retrospective cohort study included 1168 patients with an estimated glomerular filtration rate (eGFR) of 10–60 mL/min/1.73 m2 and available data on anion gap. We analyzed the association of time-updated high anion gap (anion gap ≥9.2) with the rate of cardiovascular events using marginal structural models (MSMs) to account for time-dependent confounding. We also analyzed the association between time-updated normal anion gap acidosis (anion-gap-adjusted bicarbonate level ≤22.8 mEq/L) and cardiovascular events.

Results

The mean baseline eGFR of the cohort was 28 mL/min/1.73 m2. The prevalence rates of high anion gap in CKD stages G3a, G3b, G4 and G5 were 20%, 16%, 27% and 46%, respectively. During a median follow-up period of 2.9 years, 132 patients developed cardiovascular events (3.3/100 patient-years). In MSMs, high anion gap was associated with a higher rate of cardiovascular events [hazard ratio (HR) 1.87; 95% confidence interval (95% CI) 1.13‒3.09; P = 0.02] and the composite of cardiovascular events or all-cause death (HR 3.28; 95% CI 2.19‒4.91; P < 0.001). Normal anion gap acidosis was not associated with cardiovascular events (HR 0.74; 95% CI, 0.47‒1.17; P = 0.2).

Conclusions

Among patients with advanced CKD, high anion gap was associated with an increased risk of cardiovascular events.
An unusually high upper thermal acclimation potential for rainbow trout
Authors: Adams Olivia A , Zhang Yangfan , Gilbert Matthew H , Lawrence Craig S , Snow Michael , Farrell Anthony P
Published: December 2021

Thermal acclimation, a compensatory physiological response, is central to species survival especially during the current era of global warming. By providing the most comprehensive assessment to date for the cardiorespiratory phenotype of rainbow trout (Oncorhynchus mykiss) at six acclimation temperatures from 15°C to 25°C, we tested the hypothesis that, compared with other strains of rainbow trout, an Australian H-strain of rainbow trout has been selectively inbred to have an unusually high and broad thermal acclimation potential. Using a field setting at the breeding hatchery in Western Australia, thermal performance curves were generated for a warm-adapted H-strain by measuring growth, feed conversion efficiency, specific dynamic action, whole-animal oxygen uptake (ṀO2) during normoxia and hypoxia, the critical maximum temperature and the electrocardiographic response to acute warming. Appreciable growth and aerobic capacity were possible up to 23°C. However, growth fell off drastically at 25°C in concert with increases in the time required to digest a meal, its total oxygen cost and its peak ṀO2. The upper thermal tipping points for appetite and food conversion efficiency corresponded with a decrease in the ability to increase heart rate during warming and an increase in the cost to digest a meal. Also, comparison of upper thermal tipping points provides compelling evidence that limitations to increasing heart rate during acute warming occurred well below the critical thermal maximum (CTmax) and that the faltering ability of the heart to deliver oxygen at different acclimation temperatures is not reliably predicted by CTmax for the H-strain of rainbow trout. We, therefore, reasoned the remarkably high thermal acclimation potential revealed here for the Australian H-strain of rainbow trout reflected the existing genetic variation within the founder Californian population, which was then subjected to selective inbreeding in association with severe heat challenges. This is an encouraging discovery for those with conservation concerns for rainbow trout and other fish species. Indeed, those trying to predict the impact of global warming should more fully consider the possibility that the standing intra-specific genetic variation within a fish species could provide a high thermal acclimation potential, similar to that shown here for rainbow trout.
MicroRNA and Gut Microbiota: Tiny but Mighty—Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics
Authors: Casado-Bedmar Maite , Viennois Emilie
Published: December 2021

MicroRNAs [miRNAs], small non-coding RNAs, have recently been described as crucial contributors to intestinal homeostasis. They can interact with the gut microbiota in a reciprocal manner and deeply affect host health status, leading to several disorders when unbalanced. Inflammatory bowel disease [IBD] is a chronic inflammation of the gastrointestinal tract that co-occurs with alterations of the gut microbiota, and whose aetiology remains largely unclear. On one hand, host miRNA could be playing a relevant role in IBD pathophysiology by shaping the gut microbiota. The gut microbiome, on the other hand, may regulate the expression of host miRNAs, resulting in intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation. Interestingly, it has been hypothesised that their reciprocal impact may be used for therapeutic goals. This review describes the latest research and suggests mechanisms through which miRNA and intestinal microbiota, as joint actors, may participate specifically in IBD pathophysiology. Furthermore, we discuss the diagnostic power and therapeutic potential resulting from their bidirectional communication after faecal transplantation, probiotics intake, or anti-miRNAs or miRNA mimics administration. The current literature is summarised in the present work in a comprehensive manner, hoping to provide a better understanding of the miRNA-microbiota cross-talk and to facilitate their application in IBD.
Adding historical high-sensitivity troponin T results to rule out acute myocardial infarction
Authors: Roos Andreas , Mohammad Moman A , Ekelund Ulf , Mokhtari Arash , Holzmann Martin J
Published: December 2021

Aims 

The clinical usefulness of historical concentrations of high-sensitivity cardiac troponin T (hs-cTnT) is unknown. This study investigated the ability to rule out myocardial infarction (MI) with the use of historical hs-cTnT concentrations among patients with chest pain in the emergency department (ED).

Methods and results 

The derivation cohort consisted of patients presenting with chest pain to nine different EDs (n = 60 071), where we included those with ≥1 hs-cTnT analysed at the index visit and ≥1 hs-cTnT results prior to the visit. We developed an algorithm to rule out MI within 30 days with a pre-specified target negative predictive value (NPV) of ≥99.5%. The performance was then validated in a separate cohort of ED chest pain patients (n = 10 994). A historical hs-cTnT < 12 ng/L and a < 3 ng/L absolute change between the historical and the index visit hs-cTnT had the best performance and ruled out 24 862 (41%) patients in the derivation cohort. In the validation cohort, these criteria identified 4764 (43%) low-risk patients in whom 18 (0.4%) MIs within 30 days occurred, and had an NPV for MI of 99.6% (99.4–99.8), a sensitivity of 96.9% (95.2–.2), and an LR− of 0.11 (0.07–0.14).

Conclusion 

Combining a historical hs-cTnT with a single new hs-cTnT may safely rule out MI and thereby reduce the need for serial hs-cTnT measurements in ED patients with chest pain.
Left ventricular remodelling in bicuspid aortic valve disease
Authors: Butcher Steele C , Pio Stephan M , Kong William K F , Singh Gurpreet K , Ng Arnold C T , Perry Rebecca , Sia Ching-Hui , Poh Kian Keong , Almeida Ana G , González Ariana , Shen Mylène , Yeo Tiong Cheng , Shanks Miriam , Popescu Bogdan A , Galian Gay Laura , Fijałkowski Marcin , Liang Michael , Tay Edgar , Ajmone Marsan Nina , Selvanayagam Joseph , Pinto Fausto , Zamorano Jose L , Pibarot Philippe , Evangelista Arturo , Bax Jeroen J , Delgado Victoria
Published: December 2021

Aims

Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction.

Methods and results

In this international, multicentre BAV registry, 1345 patients [51.0 (37.0–63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00–1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11–1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06–2.23, P = 0.024; HR 1.68, 95% CI 1.17–2.42, P = 0.005; HR 1.59, 95% CI 1.03–2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35–4.60, P = 0.004 and HR 3.05, 95% CI 1.71–5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD.

Conclusions

LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.
Determinants of altered left ventricular suction in pre-capillary pulmonary hypertension
Authors: Chiba Yasuyuki , Iwano Hiroyuki , Tsuneta Satonori , Tsujinaga Shingo , Meyers Brett , Vlachos Pavlos , Ishizaka Suguru , Motoi Ko , Aoyagi Hiroyuki , Tamaki Yoji , Tanemura Asuka , Murayama Michito , Yokoyama Shinobu , Nakabachi Masahiro , Nishino Hisao , Kaga Sanae , Kamiya Kiwamu , Ohira Hiroshi , Tsujino Ichizo , Anzai Toshihisa
Published: December 2021

Aims

Although the left ventricular (LV) dysfunction in pre-capillary pulmonary hypertension (PH) has been recently recognized, the mechanism of LV dysfunction in this entity is not completely understood. We thus aimed to elucidate the determinants of intraventricular pressure difference (IVPD), a measure of LV suction, in pre-capillary PH.

Methods and results

Right heart catheterization and echocardiography were performed in 86 consecutive patients with pre-capillary PH (57 ± 18 years, 85% female). IVPD was determined using colour M-mode Doppler to integrate the Euler equation. In overall, IVPD was reduced compared to previously reported value in normal subjects. In univariable analyses, QRS duration (P = 0.028), LV ejection fraction (P = 0.006), right ventricular (RV) end-diastolic area (P < 0.001), tricuspid annular plane systolic excursion (P = 0.004), and LV early-diastolic eccentricity index (P = 0.009) were associated with IVPD. In the multivariable analyses, RV end-diastolic area and LV eccentricity index independently determined the IVPD.

Conclusion

Aberrant ventricular interdependence caused by RV enlargement could impair the LV suction. This study first applied echocardiographic IVPD, a reliable marker of LV diastolic suction, to investigate the mechanism of LV diastolic dysfunction in pre-capillary PH.
Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis
Authors: Kramer Adam I , Akioyamen Leo E , Lee Seohyuk , Bélanger Alexandre , Ruel Isabelle , Hales Lindsay , Genest Jacques , Brunham Liam R
Published: December 2021

Aims

Homozygous familial hypercholesterolaemia (HoFH) is a genetic condition characterized by extremely elevated levels of low-density lipoprotein cholesterol and premature atherosclerotic cardiovascular disease and death. Due to its rarity, accurate assessment of cardiovascular outcomes associated with HoFH and how they have changed over time has been challenging. The goal of this study was to assess the prevalence and age-of-onset of major adverse cardiovascular events (MACE) among patients with HoFH.

Methods and results

We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Scopus, Africa-Wide, Google Scholar, Open Grey, and various clinical trial registries from inception to February 2020 to identify studies reporting on MACE in HoFH patients. We determined the pooled prevalence and mean age-of-onset of MACE outcomes individually using a random effects inverse variance model. We identified 94 studies that met our eligibility criteria. Myocardial infarction and coronary revascularization were common with a prevalence of 15.1% [95% confidence interval (95% CI) 10.7–20.0] and 28.3% (95% CI 22.5–34.3), respectively. The mean age-of-onset was 24.5 (95% CI 19.2–29.8) years for myocardial infarction and 32.2 (95% CI 26.6–37.8) years for revascularization. Sub-group analyses based on the year of publication revealed significant delays in the onset of MACE outcomes post-1990 compared to pre-1990. Egger’s regression suggested possible bias, likely due to small study effects.

Conclusions

Atherosclerotic cardiovascular disease is common among HoFH patients and occurs at a young age. Age-of-onset of myocardial infarction was delayed by more than a decade from pre-1990 to post-1990, likely attributable to widespread use of statins and other therapies, reflecting substantial progress in the management of this rare but severe disorder.
A term-based and citation network-based search system for COVID-19
Authors: Zerva Chrysoula , Taylor Samuel , Soto Axel J , Nguyen Nhung T H , Ananiadou Sophia
Published: December 2021

The COVID-19 pandemic resulted in an unprecedented production of scientific literature spanning several fields. To facilitate navigation of the scientific literature related to various aspects of the pandemic, we developed an exploratory search system. The system is based on automatically identified technical terms, document citations, and their visualization, accelerating identification of relevant documents. It offers a multi-view interactive search and navigation interface, bringing together unsupervised approaches of term extraction and citation analysis. We conducted a user evaluation with domain experts, including epidemiologists, biochemists, medicinal chemists, and medicine students. In general, most users were satisfied with the relevance and speed of the search results. More interestingly, participants mostly agreed on the capacity of the system to enable exploration and discovery of the search space using the graph visualization and filters. The system is updated on a weekly basis and it is publicly available at http://www.nactem.ac.uk/cord/.
LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis
Authors: Pan Zhen-Nan , Liu Jing-Cai , Ju Jia-Qian , Wang Yue , Sun Shao-Chen
Published: December 2021

Leucine-rich-repeat kinase 2 (LRRK2) belongs to the Roco GTPase family and is a large multidomain protein harboring both GTPase and kinase activities. LRRK2 plays indispensable roles in many processes, such as autophagy and vesicle trafficking in mitosis. In this study, we showed the critical roles of LRRK2 in mammalian oocyte meiosis. LRRK2 is mainly accumulated at the meiotic spindle periphery during oocyte maturation. Depleting LRRK2 led to the polar body extrusion defects and also induced large polar bodies in mouse oocytes. Mass spectrometry analysis and co-immunoprecipitation results showed that LRRK2 was associated with several actin-regulating factors, such as Fascin and Rho-kinase (ROCK), and depletion of LRRK2 affected the expression of ROCK, phosphorylated cofilin, and Fascin. Further analysis showed that LRRK2 depletion did not affect spindle organization but caused the failure of spindle migration, which was largely due to the decrease of cytoplasmic actin filaments. Moreover, LRRK2 showed a similar localization pattern to mitochondria, and LRRK2 was associated with several mitochondria-related proteins. Indeed, mitochondrial distribution and function were both disrupted in LRRK2-depleted oocytes. In summary, our results indicated the critical roles of LRRK2 in actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.
Electron microscopy for polymer structures
Authors: Jinnai Hiroshi
Published: December 2021

This paper reviews recent advances and perspectives of electron microscopy and its application to polymer hierarchical structures. Of the various kinds of hierarchical polymer structures, we placed particular emphasis on polymer nanocomposites and polymer crystals based mainly on our recent results. In those nanocomposites, the chemical bonding between the nanometer-size fillers and rubber matrix, a key contributor to the mechanical properties of the material, has been investigated by combining scanning transmission electron microscopy (STEM) with electron energy-loss spectroscopy (EELS). The position-dependent EELS spectrum with high spatial resolution of STEM successfully provided revealed the presence/absence of the chemical bonds across the interface. The mechanical properties and fracture mechanism of nanocomposites have been studied by combining structural observations made using transmission electron microscopy (TEM) with simulations. They have been further investigated using in situ TEM with a newly designed stretching holder, in which morphological changes, including cavity formation, were visualized and analyzed in terms of local strain distribution. The fracture processes of nanocomposite have been observed at nanometer resolution. The fundamental reinforcement mechanisms have been elucidated from morphological studies of nanocomposites under tensile deformation and during the fracture process. Moreover, nano-diffraction imaging, a position-resolved electron diffraction imaging with STEM, has been applied to a polymer crystal to evaluate the orientation of lamellar crystals at nanometer resolution. All these recent successes with radiation-sensitive polymer materials stemmed from developments made in electron optics and super-sensitive cameras used for advanced electron microscopy.
Holding All the Cards: Nuclear Suppliers and Nuclear Reversal
Authors: Koch Lisa Langdon
Published: December 2021

Do international nonproliferation institutions affect the decisions states make about their nuclear weapons programs? Most studies of nuclear reversal analyze outcomes, rather than decisions. However, states do not uniformly pursue nuclear weaponization but proceed along different paths lined by decisions affecting state resources, research and development, and materials and production. These decisions, which may delay or undermine a program, are critically important to understanding nuclear proliferation processes and outcomes. Using a new data set of non-termination nuclear reversal decisions across three key aspects of program development, I capture more of the process of nuclear reversal. I investigate whether two major nonproliferation institutions, the Nuclear Suppliers Group (NSG) and the Nuclear Nonproliferation Treaty (NPT), influence state decisions about whether to continue investing in ongoing programs. I argue that NSG members have strengthened cooperation across three distinct policy eras and find that the NGS's market controls have generated material constraints that raise the likelihood that states will make nuclear reversal decisions. I do not find evidence that the NPT contributes to reversal decisions within the context of ongoing programs. These findings have implications for the impact of international institutions on state behavior and for counterproliferation policy effectiveness.
Potentially Pathogenic Organisms in Stools and Their Association With Acute Diarrheal Illness in Children Aged <2 Years
Authors: Mihala Gabor , Ware Robert S , Lambert Stephen B , Bialasiewicz Seweryn , Whiley David M , Sarna Mohinder , Sloots Theo P , Nissen Michael D , Grimwood Keith
Published: December 2021

Background

Acute diarrheal illness (ADI) causes a substantial disease burden in high-income countries. We investigated associations between potentially pathogenic organisms in stools and ADI by polymerase chain reaction (PCR) in Australian children aged <2 years.

Methods

Children in a community-based birth cohort had gastrointestinal symptoms recorded daily and stool samples collected weekly until their second birthday. Diarrhea was defined as ≥3 liquid or looser than normal stools within a 24-hour period. PCR assays tested for 11 viruses, 5 bacteria, and 4 protozoa. Detections of a new organism or of the same following at least 2 negative tests were linked to ADIs, and incidence rates and estimates of association with ADI were calculated.

Results

One hundred fifty-four children provided 11 111 stool samples during 240 child-years of observation, and 228 ADIs were linked to samples. Overall, 6105 (55%) samples tested positive for a target organism. The incidence rate of 2967 new detections was 11.9 (95% confidence interval 11.4-12.3) per child-year, with 2561 (92%) new detections unrelated to an ADI. The relative risk of an ADI was 1.5-6.4 times greater for new detections of adenovirus, enterovirus, norovirus GII, parechovirus A, wild-type rotavirus, sapovirus GI/II/IV/V, Salmonella, Blastocystis, and Cryptosporidium, compared to when these were absent.

Conclusions

Wild-type rotavirus, norovirus GII, sapovirus GI/II/IV/V, adenovirus 40/41, and Salmonella were associated with ADI in this age group and setting. However, high levels of asymptomatic shedding of potential pathogens in stools from children may contribute to diagnostic confusion when children present with an episode of ADI.
Dedifferentiated liposarcoma of small bowel mesentery: a rare case report
Authors: Dhakal Sunil , Prajapati Ijendra
Published: December 2021

Liposarcoma is a common occurrence over retroperitoneum. However, dedifferentiated liposarcoma is an uncommon variety affecting the small bowel mesentery, making it a rarity. We report a case of 56-year-old male presented with the lump in the abdomen. Computed tomography abdomen revealed well-defined space-occupying lesion. Laparotomy was done and mass was excised along with segment of ileum to achieve negative margin. Histopathology and immunohistochemical study helped in determining mass to be dedifferentiated liposarcoma of mesentery. Therefore, liposarcoma should be considered in differential diagnosis of abdominal mesenchymal tumors. Surgical resection to achieve negative margin is the mainstay of treatment for mesenteric liposarcomas.
Determinants of health
Authors: Fisher Matthew , Townsend Belinda , Harris Patrick , Schram Ashley , Baum Fran
Published: December 2021

The determinants of health are the biological, psychological, behavioural, social, economic, and environmental factors that determine the health of individuals and populations. Socially or politically conditioned inequalities in the distribution of determinants lead to inequities in health within or between countries. The ways that determinants act on health are complex, involving interactions between factors and effects occurring over differing timespans. These complexities present challenges for research and public policy, to understand and take action on determinants, to improve population health, and/or to reduce health inequities. In this chapter we review the four main categories of biological, behavioural, social, and environmental determinants. We then discuss the topic of social determinants of health in more detail and review a number of the main factors identified in contemporary public health literature; from education, employment, and gender to determinants of Indigenous health, and commercial determinants of health. In a later section of the chapter (‘The complexity of determinants and their interactions’) we look at some of the challenges raised by the complex, multifactorial nature of determinants of health for research, health practice, and policy action. In the final section, we discuss two particular political challenges facing governments and international bodies seeking to take action on determinants of health and health equity.
Politics of public health
Authors: McBride Kaitlyn B. , Rosenstock Linda
Published: December 2021

The aim of public health is to improve and protect individuals and their communities, as well as promote evidence-based policy to drive decision-making across the larger health system. Researchers in academic institutions, government agencies, and the private sector provide the science to help policymakers make evidence-based health policy decisions, such as interventions to increase smoking cessation, or policies to improve access to preventive care services. In an ideal world, science (or evidence) drives policy, with politics playing a minimal or enabling role. However, this formula recognizes that public health policy is not only decided based on science (or evidence), but science itself is increasingly vulnerable to the political process, and to attacks by a wide array of players (e.g. politicians, industry leaders, and interest groups) that have vested interests to undermine scientific evidence in order to thwart the actions that would credibly follow that knowledge. Put differently, politics are key—and can be systematically analysed—in advancing or thwarting evidence-based policy.
Water and sanitation
Authors: Clasen Thomas
Published: December 2021

The lack of safe drinking water and basic sanitation impose a heavy health burden, especially on young children and the poor; it also aggravates malnutrition, physical, and cognitive development, school absenteeism, poverty, and economic development. Unlike many of the other challenges in public health, water, and sanitation solutions are well known. However, despite strong evidence of the effectiveness and cost-effectiveness of improved water and sanitation against diarrhoea and other diseases and support for the intervention at the highest levels, coverage still lags behind international targets, especially for sanitation. This chapter describes the aetiological agents of the leading water- and sanitation-related diseases, presents the evidence concerning the effectiveness of water and sanitation interventions to prevent such diseases, and summarizes the economic implications of such interventions and some of the other non-health benefits associated therewith. The chapter closes with a discussion of some of the continuing challenges in water and sanitation, including efforts to scale up interventions among the most vulnerable populations in an effort to secure the benefits of water and sanitation for all.
Food and nutrition
Authors: Shrimpton Roger , Sanders David , Thow Anne Marie
Published: December 2021

Nutrition paradigms have shifted in the last few decades, and now there is an urgent need for the policy discourse and public health practice to catch up. Effective public health policy and practice responses to nutrition depend on an accurate understanding of the problem of ‘malnutrition’, its implications for human health, and its underlying causes. They also depend on the political economy of nutrition policy—including policies relating to food environments and the global food system. The aim of this chapter is to map out the public health dimensions of food and nutrition problems that increasingly assail the world as well as to provide some guidance on the population-based interventions necessary for diet-related diseases to be contained.
Leadership in public health
Authors: Fenton Kevin A.
Published: December 2021

This chapter explores the concepts of leadership relevant to and as applied in public health practice. It looks at various concepts of leadership, frameworks for developing public health leaders, leadership development, and explores how one’s leadership practice and values evolve across their career and life course. It draws upon examples and case studies of public health leadership at global, national, and local levels; in a variety of organizations; and in various contexts to illustrate the diversity of leadership challenges, approaches, and applications. As with other public health skills, effective leadership may be taught, evaluated, and developed, with an individual’s comfort and competence with their preferred and alternative leadership styles evolving over time. This is however highly dependent upon one’s professional ambition, engagement, experience, environment, opportunities, and challenges, both in professional and private spheres. The chapter ends by exploring the principles of authentic leadership, reinforcing the importance of practitioners, at whatever phase in their career, understanding their core values, life purpose, and aligning with their day-to-day practices and the organization’s priorities. While not everyone will currently or ever be in a senior executive leadership role, many aspire to do so at some stage in their career, and everyone working in public health will be called upon to lead an activity at some stage—whether a project, administrative task, strategy, or analysis. So, leadership is ultimately everyone’s business, and the time to prepare by laying strong foundations is now. Leadership is a craft that can be learnt, nurtured, and shared, but it will be for the individual to decide when, where and how they are being called to do so, and ultimately what their answer will be.
Ethical principles and ethical issues in public health
Authors: Kass Nancy , Paul Amy , Siegel Andrew
Published: December 2021

Public health ethics considers moral dimensions of public health practice and research. While medical ethics dates back hundreds of years, and bioethics writings emerged in the 1960s and 1970s, ‘public health ethics’, articulated as such, did not appear significantly in the literature for several more decades. There has been great interest recently in defining public health ethics, examining how it resembles or differs from medical ethics or bioethics, outlining frameworks and codes, and providing conceptual and practical guidance on how ethics can inform public health practice and research. This chapter describes the emergence of public health ethics; work in bioethics with relevance for public health; the relevance of social justice theory in addressing public health problems; and discusses literature on ethics and public health research, including whether public health research ethics might differ from ethical guidance for other human research. The chapter concludes with an overview of ethics issues related to genetic research and emerging technologies.
The right to health supports global public health
Authors: Williams Carmel , Blaiklock Alison , Hunt Paul
Published: December 2021

In this chapter, we explain how human rights, including the right to health, are important for global public health. We introduce key human rights concepts and principles, and illustrate three approaches to the right to health: judicial, policy, and empowerment. We propose that human rights and public health are natural allies with a complementary and supportive relationship. We describe the meaning of the right to the highest attainable standard of health and its place in international, regional, and national laws. We outline ten key elements of the right to health and how the right can be operationalized in public health practice. We demonstrate this with two case studies of critically important global public health issues—climate change and children’s health, and overseas development assistance—as well as one of an emerging challenge in health, the digitization of health through Big Data.
Law and the public’s health
Authors: Gostin Lawrence O.
Published: December 2021

Public health law safeguards the health and safety of the population, promoting the human right to life and health, and the realization of social justice. There is sometimes a tension between public health regulation to promote community health and protecting individual liberty and autonomy. Governments must balance the common good with individual freedoms. In many countries, there are constitutional rights to health or to life that provide a positive duty on government to advance the right to health. Governments have multiple legal tools available to improve the public’s health and safety, ranging from the economic power to tax and spend, to the authority to alter the environments in which people live, through to direct and indirect regulation, including, where necessary, deregulation. Although the law can be a powerful agent for change, intervention can also raise critical social, ethical, or constitutional concerns. These issues are illustrated through four brief case studies on infectious diseases, non-communicable diseases, unintentional injuries, and violence to self or others.
Public health policy in developed countries
Authors: Powles John , Gouda Hebe
Published: December 2021

Public health policies might thus be thought of as the policies that guide these ‘organized efforts’ to protect and improve health. The scope of such policies depends a good deal, however, on what is considered to be entailed by ‘organized efforts’. and on how centrally ‘organized efforts’ are understood to be related to efforts that are more decentralized, more informal, less organized, perhaps even ‘spontaneous’. The relative importance and legitimacy of centralized versus decentralized uses of knowledge in protecting and enhancing health is a common underlying theme in discussion of public health policy. This chapter discusses public health policy, and differences in outcomes, across different developed countries.
Qualitative research imagination
Authors: Popay Jennie , Baum Fran
Published: December 2021

In this chapter we will consider what the qualitative research imagination ‘is’—touching on key questions that should be addressed by all researchers regardless of their approach.) In the first part of the chapter we will consider the first two questions focusing on the type of ‘knowledge’ generated by qualitative research and in the second part on questions about the range of approaches that can be taken to data collection, analysis and interpretation, and the role of theory. The rest of this chapter is divided into three parts. First, we discuss the type of knowledge produced by qualitative research. We then discuss the potential for community/public involvement as ‘partners’ in qualitative research and finally consider key methodological issues in the conduct of qualitative research.
Methodological issues in the design and analysis of cluster randomized trials
Authors: Baisley Kathy J. , Hayes Richard J. , Moulton Lawrence H.
Published: December 2021

Randomized controlled trials are the accepted gold standard for evaluating the effects of interventions to improve health. In the majority of such trials, individuals are randomly allocated to the experimental conditions under study, for example, to treatment and control arms. However, in some situations it is more appropriate to randomly allocate groups of individuals to the treatment arms. These groups are referred to as clusters, and trials of this kind are known as cluster randomized trials (CRTs). Examples of clusters include schools, villages, workplaces, or health facilities, but there are many other possible choices. In some CRTs, all individuals within the selected clusters are automatically included. In others, there may be additional eligibility criteria. Similarly, the impact of the intervention may be measured in all individuals in the cluster, or in a random subsample. This chapter aims to discuss methodological issues that arise in the design and analysis of CRTs
Validity and bias in epidemiological research
Authors: Greenland Sander , VanderWeele Tyler J.
Published: December 2021

Some of the major concepts of validity and bias in epidemiological research are outlined in this chapter. The contents are organized in four main sections: Validity in statistical interpretation, validity in prediction problems, validity in causal inference, and special validity problems in case–control and retrospective cohort studies. Familiarity with the basics of epidemiological study design and a number of terms of epidemiological theory, among them risk, competing risks, average risk, population at risk, and rate, is assumed. Despite similarities, there is considerable diversity and conflict among the classification schemes and terminologies employed in various textbooks. This diversity reflects that there is no unique way of classifying validity conditions, biases, and errors. It follows that the classification schemes employed here and elsewhere should not be regarded as anything more than convenient frameworks for organizing discussions of validity and bias in epidemiological inference. Several important study designs, including randomized trials, prevalence (cross-sectional) studies, and ecological studies, are not discussed in this chapter. Such studies require consideration of the validity conditions mentioned earlier and also require special considerations of their own. A number of central problems of epidemiological inference are also not covered, including choice of effect measures, problems of induction, and causal modelling.
Statistical methods
Authors: Williams Gail , Ware Robert S.
Published: December 2021

This chapter provides an introduction to statistical methods with illustrative examples from public health and epidemiological research. The chapter begins by distinguishing between a study sample and a target population. It goes on to outline different methods of sampling, including probability and non-probability sampling methods. In the following section, the distributions of epidemiological variables are considered, leading on to discussion of probability distributions and statistical inference. Methods for comparing data from two or more groups are then outlined, including methods for continuous and categorical variables. Analysis of time-to-event data to evaluate survival times is then outlined. The final section of the chapter discusses the application of multivariable models to epidemiological data, including extensions of basic models to more complex data distributions. The chapter concludes by cautioning that increasing ease of access to sophisticated statistical methods may increase the risk of erroneous application. There is little substitute for consulting a qualified statistician, particularly with complex designs.