A Likelihood-Based Approach with Shared Latent Random Parameters for the Longitudinal Binary and Informative Censoring Processes

Longitudinal studies with binary outcomes characterized by informative right censoring are commonly encountered in clinical, basic, behavioral, and health sciences. Approaches developed to analyze data with binary outcomes were mainly tailored to clustered or longitudinal data with missing completely at random or at random. Studies that focused on informative right censoring with binary outcomes are characterized by their imbedded computational complexity and difficulty of implementation. Here we present a new maximum likelihood-based approach with repeated binary measures modeled in a generalized linear mixed model as a function of time and other covariates. The longitudinal binary outcome and the censoring process determined by the number of times a subject is observed share latent random variables (random intercept and slope) where these subject-specific random effects are common to both models. A simulation study and sensitivity analysis were conducted to test the model under different assumptions and censoring settings. Our results showed accuracy of the estimates generated under this model when censoring was fully informative or partially informative with dependence on the slopes. A successful implementation was undertaken on a cohort of renal transplant patients with blood urea nitrogen as a binary outcome measured over time to indicate normal and abnormal kidney function until the emanation of graft rejection that eventuated in informative right censoring. In addition to its novelty and accuracy, an additional key feature and advantage of the proposed model is its viability of implementation on available analytical tools and widespread application on any other longitudinal dataset with informative censoring.

     

Humidifier Disinfectants Are a Cause of Lung Injury among Adults in South Korea: A Community-Based Case-Control Study

Backgrounds

An outbreak of lung injury among South Korean adults was examined in a hospital-based case-control study, and the suspected cause was exposure to humidifier disinfectant (HD). However, a case-control study with community-dwelling controls was needed to validate the previous study’s findings, and to confirm the exposure-response relationship between HD and lung injury.

Methods

Each case of lung injury was matched with four community-dwelling controls, according to age (±3 years), sex, residence, and history of childbirth since 2006 (for women). Environmental risk factors, which included type and use of humidifier and HD, were investigated using a structured questionnaire during August 2011. The exposure to HD was calculated for both cases and controls, and the corresponding risks of lung injury were compared.

Results

Among 28 eligible cases, 16 patients agreed to participate, and 60 matched controls were considered eligible for this study. The cases were more likely to have been exposed to HD (odds ratio: 116.1, 95% confidence interval: 6.5–2,063.7). All cases were exposed to HDs containing polyhexamethyleneguanidine phosphate, and the risk of lung injury increased with the cumulative exposure, duration of exposure, and exposure per day.

Conclusions

This study revealed a statistically significant exposure-response relationship between HD and lung injury. Therefore, continuous monitoring and stricter evaluation of environmental chemicals’ safety should be conducted.     

Active‐Site Imprinting: Preparation of Fe–N–C Catalysts from Zinc Ion–Templated Ionothermal Nitrogen‐Doped Carbons

Atomically dispersed Fe–N–C catalysts are considered the most promising precious‐metal‐free alternative to state‐of‐the‐art Pt‐based oxygen reduction electrocatalysts for proton‐exchange membrane fuel cells. The exceptional progress in the field of research in the last ≈30 years is currently limited by the moderate active site density that can be obtained. Behind this stands the dilemma of metastability of the desired FeN₄ sites at the high temperatures that are believed to be a requirement for their formation. It is herein shown that Zn²⁺ ions can be utilized in the novel concept of active‐site imprinting based on a pyrolytic template ion reaction throughout the formation of nitrogen‐doped carbons. As obtained atomically dispersed Zn–N–Cs comprising ZnN₄ sites as well as metal‐free N₄ sites can be utilized for the coordination of Fe²⁺ and Fe³⁺ ions to form atomically dispersed Fe–N–C with Fe loadings as high as 3.12 wt%. The Fe–N–Cs are active electocatalysts for the oxygen reduction reaction in acidic media with an onset potential of E₀ = 0.85 V versus RHE in 0.1 m HClO₄. Identical location atomic resolution transmission electron microscopy imaging, as well as in situ electrochemical flow cell coupled to inductively coupled plasma mass spectrometry measurements, is employed to directly prove the concept of the active‐site imprinting approach.     

G Protein betagamma subunits augment UVB-induced apoptosis by stimulating the release of soluble heparin-binding epidermal growth factor from human keratinocytes

UV radiation induces various cellular responses by regulating the activity of many UV-responsive enzymes, including MAPKs. The betagamma subunit of the heterotrimeric GTP-binding protein (Gbetagamma) was found to mediate UV-induced p38 activation via epidermal growth factor receptor (EGFR). However, it is not known how Gbetagamma mediates the UVB-induced activation of EGFR, and thus we undertook this study to elucidate the mechanism. Treatment of HaCaT-immortalized human keratinocytes with conditioned medium obtained from UVB-irradiated cells induced the phosphorylations of EGFR, p38, and ERK but not that of JNK. Blockade of heparin-binding EGF-like growth factor (HB-EGF) by neutralizing antibody or CRM197 toxin inhibited the UVB-induced activations of EGFR, p38, and ERK in normal human epidermal keratinocytes and in HaCaT cells. Treatment with HB-EGF also activated EGFR, p38, and ERK. UVB radiation stimulated the processing of pro-HB-EGF and increased the secretion of soluble HB-EGF in medium, which was quantified by immunoblotting and protein staining. In addition, treatment with CRM179 toxin blocked UV-induced apoptosis, but HB-EGF augmented this apoptosis. Moreover, UVB-induced apoptosis was reduced by inhibiting EGFR or p38. The overexpression of Gbeta(1)gamma(2) increased EGFR-activating activity and soluble HB-EGF content in conditioned medium, but the sequestration of Gbetagamma by the carboxyl terminus of G protein-coupled receptor kinase 2 (GRK2ct) produced the opposite effect. The activation of Src increased UVB-induced, Gbetagamma-mediated HB-EGF secretion, but the inhibition of Src blocked that. Overexpression of Gbetagamma increased UVB-induced apoptosis, and the overexpression of GRK2ct decreased this apoptosis. We conclude that Gbetagamma mediates UVB-induced human keratinocyte apoptosis by augmenting the ectodomain shedding of HB-EGF, which sequentially activates EGFR and p38.     

Histopathology of the pterygium in population on Croatian Island Rab

In the 1975-2004 period, 130 cases of pterygium were estimated, 83 males and 47 females, on a small island Rab. Island Rab is located in the north part of the Adriatic sea, which has very high index of sun radiation. Pterygium is usually histopathologically defined as a hyperplasia of conjunctival tissue, elastoid degeneration of subepithelieum and fragmentation of Bowman's membrane. Our histopathological findings in 73 eyes are following: conjunctiva with neovascularisation, leukocyte margination and subepithelial basophilic degeneration, proliferation of conjunctival tissue, acanthosis and squamous metaplasia, and mucinous elements, focaly present plasma cells, focuses of increased pigmentisation in basal epithelial layers, tenon capsule with edema, diffuse neovascularisation and fragmentation of fibrils. These findings suggest that in severe cases of pterygium histopathologically exists precancerosis. In conclusion, on the basis of these histopathological findings, especially in the Tenon capsule, we suggest that for surgical procedure of pterygium the excision of the Tenon capsule, extensively under pterygium, is necessary.     

Sunlight and incidence of pterygium on Croatian Island Rab--epidemiological study

The aim of this epidemiologic study, on small island Rab, in North Adriatic Sea, is to estimate correlation between climatic factors, specially chronic exposure to strong visible and UV light, and appearance of pterygium and exfoliation syndrome. In the first group of population which live in a village and who are agriculturists and fishermen (480 persons) appearance of pterygium is in 23% (16% in males and 7% in females), but 0.0% in urban people (61 people). The appearance of exfoliation syndrome was in the first group of agriculturists and fishermen population in 21%, of which 19% of males and 2% of females, and in urban people 0.0%. The higher intraocular pressure in exfoliation syndrome was 92%. All population in this examination were in the highest age (mean age is 65-80 years). Chronic exposure to sunlight caused the high percentage appearance of pterygium and exfoliation syndrome.     

Propane-associated autoerotic asphyxiation: accident or suicide?

Autoerotic fatalities refer to a death resulting from the participation in a sex-related activity designed to heighten sexual arousal. The overwhelming majority of these deaths are due to asphyxia, most often by hanging or ligature compression of the neck. Here we report a case of "atypical" autoerotic fatality in which death was not induced by ligature compression. Unusual death of a 24-year-old man, involving propane inhalation and plastic bag suffocation, is described. The special characteristics of propane gas as an asphyxiant agent are discussed, as well as its effect on the human body.     

Raiders of the lost bark: orangutan foraging strategies in a degraded landscape

Deforestation is rapidly transforming primary forests across the tropics into human-dominated landscapes. Consequently, conservationists need to understand how different taxa respond and adapt to these changes in order to develop appropriate management strategies. Our two year study seeks to determine how wild Sumatran orangutans (Pongo abelii) adapt to living in an isolated agroforest landscape by investigating the sex of crop-raiders related to population demographics, and their temporal variations in feeding behaviour and dietary composition. From focal animal sampling we found that nine identified females raided cultivated fruits more than the four males. Seasonal adaptations were shown through orangutan feeding habits that shifted from being predominantly fruit-based (56% of the total feeding time, then 22% on bark) to the fallback food of bark (44%, then 35% on fruits), when key cultivated resources such as jackfruit (Artocarpus integer), were unavailable. Cultivated fruits were mostly consumed in the afternoon and evening, when farmers had returned home. The finding that females take greater crop-raiding risks than males differs from previous human-primate conflict studies, probably because of the low risks associated (as farmers rarely retaliated) and low intraspecific competition between males. Thus, the behavioral ecology of orangutans living in this human-dominated landscape differs markedly from that in primary forest, where orangutans have a strictly wild food diet, even where primary rainforests directly borders farmland. The importance of wild food availability was clearly illustrated in this study with 21% of the total orangutan feeding time being allocated to feeding on cultivated fruits. As forests are increasingly converted to cultivation, humans and orangutans are predicted to come into conflict more frequently. This study reveals orangutan adaptations for coexisting with humans, e.g. changes in temporal foraging patterns, which should be used for guiding the development of specific human-wildlife conflict mitigation strategies to lessen future crop-raiding and conflicts.     

Genetic differentiation of the Western Capercaillie highlights the importance of South-eastern Europe for understanding the species phylogeography

The Western Capercaillie (Tetrao urogallus L.) is a grouse species of open boreal or high altitude forests of Eurasia. It is endangered throughout most mountain range habitat areas in Europe. Two major genetically identifiable lineages of Western Capercaillie have been described to date: the southern lineage at the species' southernmost range of distribution in Europe, and the boreal lineage. We address the question of genetic differentiation of capercaillie populations from the Rhodope and Rila Mountains in Bulgaria, across the Dinaric Mountains to the Slovenian Alps. The two lineages' contact zone and resulting conservation strategies in this so-far understudied area of distribution have not been previously determined. The results of analysis of mitochondrial DNA control region sequences of 319 samples from the studied populations show that Alpine populations were composed exclusively of boreal lineage; Dinaric populations of both, but predominantly (96%) of boreal lineage; and Rhodope-Rila populations predominantly (>90%) of southern lineage individuals. The Bulgarian mountains were identified as the core area of the southern lineage, and the Dinaric Mountains as the western contact zone between both lineages in the Balkans. Bulgarian populations appeared genetically distinct from Alpine and Dinaric populations and exhibited characteristics of a long-term stationary population, suggesting that they should be considered as a glacial relict and probably a distinct subspecies. Although all of the studied populations suffered a decline in the past, the significantly lower level of genetic diversity when compared with the neighbouring Alpine and Bulgarian populations suggests that the isolated Dinaric capercaillie is particularly vulnerable to continuing population decline. The results are discussed in the context of conservation of the species in the Balkans, its principal threats and legal protection status. Potential conservation strategies should consider the existence of the two lineages and their vulnerable Dinaric contact zone and support the specificities of the populations.