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We reported a 10-year-old child who suffered from severe toxic epidermal necrolysis triggered by trimethoprim–sulfamethoxazole and managed successfully with multi-targeted therapy. He was jointly managed by a paediatric intensivist, a dermatologist, an otolaryngologist, a urologist, a wound nurse, a pain management specialist, a dietitian, and a clinical psychologist. Systemic intravenous immunoglobulin and pulsed-dose methylprednisolone were initiated after admission. Oral cyclosporin A was added in the early stage of the disease in view of severe ocular involvement with progressive inflammation of bilateral upper and lower eyelids, the presence of pseudomembrane, diffuse conjunctival injection, and progression of central epithelial defects in bilateral eyes. He underwent amniotic membrane transplantation. Subcutaneous injection of etanercept was added on the treatment to allow rapid tapering of steroids. Finally, the disease progression was halted with re-epithelisation on day 13. He experienced no side effects from the multi-targeted therapy and recovered well without clinical sequelae.

Background Medication errors (MEs) can lead to adverse effects and mortality, especially in older adults, due to physiological changes and accumulated multi-morbidities associated with ageing. Hence, interventions to reduce MEs among older adults are important and examining their effects will provide us with the impetus to improve upon current local measures to further reduce MEs. Objectives To review the effectiveness of the interventions that have been implemented locally to reduce MEs. Methods Using chosen keywords, searches were conducted in Pubmed and Google scholar. Based on their abstract, relevant articles were chosen from all retrieved articles that were published in English. Relevant online resources and other journal articles referenced in the chosen articles were also referenced in writing this narrative review. Results and Conclusion Although MEs occur globally, studies examining the prevalence of MEs within Asia are lacking and the impact of various local interventions to reduce MEs is also poorly understood. Electronic prescribing, a national electronic health records repository, education in geriatric pharmacotherapy, a more centralised pharmacist’s role and the use of prescribing assessment tools are local interventions whose effectiveness in reducing MEs are supported, instead, by overseas studies examining such similar interventions. Locally, more studies are needed to examine the effectiveness of interventions in reducing MEs in various settings.

Abstract Background To analyse ophthalmic presentations to an outer metropolitan and a rural emergency department (ED) during the first wave of the COVID-19 pandemic in New South Wales (NSW), Australia. Methods A retrospective comparative study of ophthalmic emergency presentations to Campbelltown Hospital (fifth busiest NSW metropolitan ED; population 310,000) and Bowral and District Hospital (rural ED; population 48,000) before and during COVID-19 was conducted. Patient demographics, triage category, referral source, diagnosis, length of stay, departure status, and follow-up location were assessed from coding data between March 1st to May 31st in 2019 and 2020, corresponding to the peak case numbers and restrictions during the first wave of the COVID-19 pandemic in NSW. Differences before and during COVID-19 were analysed using chi-squared tests or independent sample t-tests. Results There was no change in ophthalmic presentations at Campbelltown (n = 228 in 2019 vs. n = 232 in 2020; + 1.75%, p = 0.12) and an increase at Bowral (n = 100 in 2019 vs. n = 111 in 2020; + 11%, p

The location for the New Yogyakarta International Airport (NYIA) construction involved in land disputes during the land acquisition process. The land acquisition will always lead to disputes or conflicts with the affected people. It is even more complicated if, in the development process, the ruling elite intervenes, external forces outside the local community that are not directly related to the development. This article deals with the question of the government's public perceptions of the legal polemic of land dispute settlement based on Law No.2 of 2012, and concentrates to examine a new model of land dispute resolution from the perspective of affected communities against NYIA. This research is normative-empirical based on primary and secondary data, namely a literature study, field study, using purposive sampling with interviews, FGD, observation, and qualitative descriptive analysis. The result showed the failure of formal litigation and non-litigation approaches offered by Law No.2 of 2012 to resolve the disputes fairly. Village discussions based on local wisdom as a new model for equitable land dispute resolution needs a political review of Law No. 2 of 2012. The new paradigm of agrarian reform must be based on customary law and local wisdom values in the 1945 Constitution and the Agrarian Law. Given recent controversies concerning land disputes, a law on reform and structuring the national agrarian structure, Agrarian conflict resolution law, and law of natural resources management for the community are urgently needed.

This study aims to explain in detail why the dualism of local regulations testing after the amendment of the 1945 Constitution Research is also directed to provide a testing system solutions in the future regulation. Legal discourses are still academic debate is when the right of judicial review by the Supreme Court Regulation hostage by Law No. 23 of 2014 on Regional Government. Supremacy of the constitution as part of the main characteristics of the legal state impressed distorted due to the duality of the regulation testing including how the implications of the Constitutional Court Number 137 PUU-XIII / 2015 Jo Court Number 56 / PUU-XIV / 2016 on June 14, 2017 last. Position regulation as executive versus legislative product as much a part of this study in order to find the ideal solution testing legislation in the future.The research method used was a normative legal research (legal research) which is based on the study of literature or secondary data divided form the primary legal materials, secondary law material and tertiary legal materials. Models used approach is the approach of law (statute aproach) and conceptual approach (conceptual aproach). A number of secondary data collected will be analyzed by descriptive qualitative where the process used deductive thinking. To get accuracy of understanding (subtilitas itellegendi) and accuracy translating (subtilitas explicandi) to solve the problem formulation.

This study compared breast cancer survival and the prognostic factors across different age groups of women in Penang, Malaysia. Data on 2,166 women with breast cancer who had been diagnosed between 2010 and 2014 were extracted from the Penang Breast Cancer Registry and stratified into 3 age groups: young (< 40 years old), middle-aged (40-59 years old), and elderly (≥ 60 years). The overall and relative survival rates were calculated using the life table method, median survival time was calculated using the Kaplan-Meier method, and comparisons between groups were conducted using the log-rank test. Prognostic factors were analyzed using a Cox proportional hazards model. The 5-year overall and breast cancer-specific survival rates for women with breast cancer in Penang were 72.9% and 75.2%, with a mean survival time of 92.5 months and 95.1 months, respectively. The 5-year breast cancer-specific survival rates for young, middle-aged, and elderly women were 74.9%, 77.8%, and 71.4%, respectively, with a mean survival time of 95.7 months, 97.5 months, and 91.2 months. There was a significant difference in breast cancer survival between age groups, with elderly women showing the lowest survival rate, followed by young and middle-aged women. Disease stage was the most prominent prognostic factor for all age groups. Survival rates and prognostic factors differed according to age group. Treatment planning for breast cancer patients should be age-specific to promote better cancer care and survival.

This study examines, Firstly, aspects of the formation of Law Num. 2/2012. Secondly, interpretation of the meaning of development in the public interest. Thirdly, the compensation process for the release of land rights for development. Finally, polemic of MK's Decision Num. 50/PUU-X/2012. The findings show, procedural aspects of the formation of Law Num. 2/2012, is not in accordance with the rules for the formation of applicable laws. Likewise, the meaning conception of the public interest and the process of compensation for land is still far from the spirit of the Law Num. 5 of 1960 (UUPA) Jo Article 33 of the 1945 Constitution. The Post of MK's Decision Num. 50/PUU-X/2012, there needs to be a legislative review of Law Num. 2/2012, to deconstruct the meaning of “social function of the land” to conform to the philosophy of Article 33 of the 1945 Constitution and the Law Num. 5 of 1960 (UUPA). The Parliament must immediately complete the Agrarian Structure Renewal and Arrangement Bill, the Agrarian Conflict Resolution Bill, and the Natural Resource Management Bill, as mandated by MPR Decree Num. IX/2001 Jo Tap MPR Num. V/2003. Development in the public interest, must be placed in the spirit of social and agrarian reform in order to achieve maximum prosperity for the people.

It is desirable to deposit more energy in the dense plasma core to trigger the fusion ignition. Here the authors demonstrate enhanced energy coupling from laser to plasma core by using solid targets and guiding the transport of relativistic electron beam with external magnetic field.

Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH is associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired lysosomal acidification remain poorly understood. We show here that inhibition of lysosomal acidification triggers cellular iron deficiency, which results in impaired mitochondrial function and non-apoptotic cell death. These effects are recovered by supplying iron via a lysosome-independent pathway. Notably, iron deficiency is sufficient to trigger inflammatory signaling in cultured primary neurons. Using a mouse model of impaired lysosomal acidification, we observed a robust iron deficiency response in the brain, verified by in vivo magnetic resonance imaging. Furthermore, the brains of these mice present a pervasive inflammatory signature associated with instability of mitochondrial DNA (mtDNA), both corrected by supplementation of the mice diet with iron. Our results highlight a novel mechanism linking impaired lysosomal acidification, mitochondrial malfunction and inflammation in vivo.

Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Mitochondrial biogenesis and function defects in these cells are rescued by the silencing of KLF2 or ETV1. Increased ETV1 expression is regulated by KLF2, while the increase of KLF2 protein levels in NPC and ASM stems from impaired signaling downstream sphingosine-1-phosphate receptor 1 (S1PR1), which normally represses KLF2. In patient cells, S1PR1 is barely detectable at the plasma membrane and thus unable to repress KLF2. This manuscript provides a mechanistic pathway for the prevalent mitochondrial defects in lysosomal storage diseases.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

This article consists of 2 parts. The first part, from Section 1 to Section 3, by King Fai Chan aims at unravelling the inaugural ideology of Hong Kong’s political parties by going back to one of the founders of the Democratic Party, Yeung Sum, and examines his ideology of an idealistic thinking of political cooperation with the SAR government, with an aim of peaceful power-sharing. Yeung Sum’s idea of political parties is a new vision of a political subjectivity that caters to the whole, and this confirms with Giovanni Satori’s theory that an authentic party must be part-of-the-whole. In the end the idea of party as effective opposition was completely overlooked. The article then turns to the second part, from Section 4 to Section 6, by Sze Chi Chan, who aims at detailing the inauguration of an effective oppositional party after the Grand March of 2003. Thus was born the League of Social Democrats, with the second author as one of its founding members. In the second author’s portrayal the League was off to a promising start that ushered in an effective oppositional party, that did pose a series of effective political opposition that readily catered to the need of the whole citizenry, especially the Five District de facto Referendum. Yet in the end the League met with a fate of internal split that tremendously dwindled the its oppositional thrust. As yet we still do not find any pan-democratic party or anti-establishment radical party that can really demonstrate Satori’s ideal of party acting as part-of-the-whole fighting for the benefit of the whole.

The Constitutional Court Decision, Number 92/PUU-X/2012 has opened a new legislation policy for the Senate of Indonesia. The impact of this decision can strengthen legislation competence to the Senate in inisiating the legal drafting, as attributed on Article 22D of the 1945 Constitution of Republic of Indonensia. The decision can be a landmark decision for struggling the strong bicameral system and presidential system after amendment of the 1945 Constitution. As the impact of the decision, the house of representatives must soon take legislative review especially to Act Number 27 of 2009 and Act Number 12 of 2011 to accommodate the legal substance of the decision (The Constitutional Court Decision, Number 92/PUU-X/2012).

A retrospective study of 176 treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) that had undergone intravitreal aflibercept treatment (2.0 mg, 7–8 times over one year) was performed to correlate the effect of aflibercept on the morphological features of nAMD—subretinal hyper-reflective material (SHRM), pigment epithelial detachment (PED), subretinal fluid (SRF), and intraretinal fluid (IRF)—with visual acuity at baseline and at one year. Spectral-Domain Optical Coherence Tomography (SD-OCT) images and best-corrected visual acuity (BCVA) at baseline and at one year were obtained. The relationship between visual acuity and the presence of morphological features at baseline and at one year was statistically analysed. The proportion of eyes with PED (p = 0.01), SRF (p ≤ 0.001), and IRF (p ≤ 0.001) reduced at one year. SHRM (p = 0.002) and IRF (p = 0.0001) were associated with poorer baseline BCVA. The presence of SRF at baseline was associated with better baseline BCVA (p = 0.004) and 5.3 letters of improvement of BCVA after one year of treatment (p = 0.0001). For each letter increase in BCVA at baseline, 0.25 fewer letters were gained in BCVA at one year. While aflibercept can improve morphological abnormalities in nAMD, this is not always accompanied by a corresponding improvement in visual acuity.

The use of traffic simulation to analyze complex transportation issues has become common practice in transportation engineering. The further application of microsimulation to the analysis of traffic safety in a systematic, rigorous, and controlled fashion is becoming increasingly viable as simulation models improve and tools for quantifying surrogate safety measures become readily accessible. Using a calibrated traffic microsimulation model and surrogate safety assessment model analysis, this paper examined how the risk for left-turn crashes varied as traffic conditions changed at a signalized intersection. Safety impacts for 750 unique combinations of intersection geometry, traffic, and signal timing parameters were simulated and the number of left-turn conflicts per hour noted. Results of the simulation analyses were used to develop statistical models that expressed the risk of occurrence of a left-turn crash during a given hour as a function of the left-turn phasing mode and prevailing conditions during that hour. The study was motivated by the recent widespread application of the flashing yellow arrow (FYA) which provides the opportunity to vary left-turn phasing mode by time of day-potentially leading to more efficient traffic operations at signalized intersections. In this regard, the study addresses a basic need for tools that predict how the risk for left-turn crashes might vary at a more disaggregated level than that provided by existing crash prediction models, which typically predict yearly totals of left-turn crashes, often based on annual average daily traffic volumes. Potential application of the model to the implementation of a time-variable safety-based left-turn phasing selection scheme using FYA was successfully demonstrated., (Published by Elsevier Ltd.)

High temperatures resulting in physiological stress and the reduced ability to resist predation can have life-or-death consequences for an organism. We investigated the effects of temperature on the susceptibility to predation for an ectothermic intertidal mollusc (the owl limpet, Lottia gigantea ) and its predator (the black oystercatcher, Haematopus bachmani ). The ability of L. gigantea to resist bird predation during low tide is determined by the tenacity of attachment to the rock. We developed a transducer to measure the force of predatory attacks on limpets by a captive black oystercatcher, and tested the hypothesis that exposure to warm temperatures during low tide emersion would affect the limpet's ability to resist dislodgement in trials with a morphometrically accurate beak mimic and a live bird. In beak mimic trials, four times as many limpets exposed to warm low tides were removed, as compared with limpets exposed to cool low tides or in 'no low tide' submerged conditions. Minimum time before limpet removal in captive bird trials was more than six times longer for limpets in cool low tide or no low tide treatments compared with limpets in the warm low tide treatment. We measured shear forces up to 36.63 N during predatory strikes. These direct measurements of the forces exerted by a living oystercatcher provide context for interactions with multiple prey species. Our data suggest that naturally occurring variation in body temperatures among individual prey items in the field could be an important driver of predator-prey interactions and subsequently community patterns., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

By incorporating joints into their otherwise rigid fronds, erect coralline algae have evolved to be as flexible as other seaweeds, which allows them to thrive - and even dominate space - on wave-washed shores around the globe. However, to provide the required flexibility, the joint tissue of Calliarthron cheilosporioides, a representative articulated coralline alga, relies on an extraordinary tissue that is stronger, more extensible and more fatigue resistant than that of other algae. Here, we used the results from recent experiments to parameterize a conceptual model that links the microscale architecture of cell walls to the adaptive mechanical properties of joint tissue. Our analysis suggests that the theory of discontinuous fiber-wound composite materials (with cellulose fibrils as the fibers and galactan gel as the matrix) can explain key aspects of the material's mechanics. In particular, its adaptive viscoelastic behavior can be characterized by two, widely separated time constants. We speculate that the short time constant (∼14 s) results from the viscous response of the matrix to the change in cell-wall shape as a joint is stretched, a response that allows the material both to remain flexible and to dissipate energy as a frond is lashed by waves. We propose that the long time constant (∼35 h), is governed by the shearing of the matrix between cellulose fibrils. The resulting high apparent viscosity ensures that joints avoid accumulating lethal deformation in the course of a frond's lifetime. Our synthesis of experimental measurements allows us to draw a chain of mechanistic inference from molecules to cell walls to fronds and community ecology., (© 2016. Published by The Company of Biologists Ltd.)

Flexibility is key to survival for seaweeds exposed to the extreme hydrodynamic environment of wave-washed rocky shores. This poses a problem for coralline algae, whose calcified cell walls make them rigid. Through the course of evolution, erect coralline algae have solved this problem by incorporating joints (genicula) into their morphology, allowing their fronds to be as flexible as those of uncalcified seaweeds. To provide the flexibility required by this structural innovation, the joint material of Calliarthron cheilosporioides, a representative articulated coralline alga, relies on an extraordinary tissue that is stronger, more extensible and more fatigue resistant than the tissue of other algal fronds. Here, we report on experiments that reveal the viscoelastic properties of this material. On the one hand, its compliance is independent of the rate of deformation across a wide range of deformation rates, a characteristic of elastic solids. This deformation rate independence allows joints to maintain their flexibility when loaded by the unpredictable - and often rapidly imposed - hydrodynamic force of breaking waves. On the other hand, the genicular material has viscous characteristics that similarly augment its function. The genicular material dissipates much of the energy absorbed as a joint is deformed during cyclic wave loading, which potentially reduces the chance of failure by fatigue, and the material accrues a limited amount of deformation through time. This limited creep increases the flexibility of the joints while preventing them from gradually stretching to the point of failure. These new findings provide the basis for understanding how the microscale architecture of genicular cell walls results in the adaptive mechanical properties of coralline algal joints., (© 2016. Published by The Company of Biologists Ltd.)

In this review we consider how small-scale temporal and spatial variation in body temperature, and biochemical/physiological variation among individuals, affect the prediction of organisms' performance in nature. For 'normal' body temperatures - benign temperatures near the species' mean - thermal biology traditionally uses performance curves to describe how physiological capabilities vary with temperature. However, these curves, which are typically measured under static laboratory conditions, can yield incomplete or inaccurate predictions of how organisms respond to natural patterns of temperature variation. For example, scale transition theory predicts that, in a variable environment, peak average performance is lower and occurs at a lower mean temperature than the peak of statically measured performance. We also demonstrate that temporal variation in performance is minimized near this new 'optimal' temperature. These factors add complexity to predictions of the consequences of climate change. We then move beyond the performance curve approach to consider the effects of rare, extreme temperatures. A statistical procedure (the environmental bootstrap) allows for long-term simulations that capture the temporal pattern of extremes (a Poisson interval distribution), which is characterized by clusters of events interspersed with long intervals of benign conditions. The bootstrap can be combined with biophysical models to incorporate temporal, spatial and physiological variation into evolutionary models of thermal tolerance. We conclude with several challenges that must be overcome to more fully develop our understanding of thermal performance in the context of a changing climate by explicitly considering different forms of small-scale variation. These challenges highlight the need to empirically and rigorously test existing theories., (© 2015. Published by The Company of Biologists Ltd.)

The seven NIH-sponsored Regional Primate Research Centers conduct a wide variety of studies in the neurosciences and on aging. Monkeys and chimpanzees are investigated to validate the results of research obtained with lower species. In addition, primates are often the only species with the appropriate characteristics for studying a particular health problem or certain behavioral or biological principles. One neurological disorder for which the primate model has proven crucial is Parkinson's disease. The surgical implantation of dopaminergic cells and tissue containing a growth factor has been developed in the primate model, and is now being evaluated clinically in humans with Parkinsonism. In addition to neurological diseases such as Parkinson's, multiple sclerosis, and epilepsy, the visual system is a strong focus of basic and applied research at the Centers. In 1981, two neuroscientists whose basic research on vision with application to pediatric ophthalmology took place in part at the New England Regional Primate Research Center, were honored with the Nobel Prize in Physiology and Medicine. Currently, vision studies at the Yerkes Regional Primate Research Center, for example, focus on myopia, post-surgical treatment of congenital cataracts, adult cataract development and treatment, and laser surgery to correct corneal abnormalities. At the Wisconsin Regional Primate Research Center, the role of diet in visual impairment is evaluated during infancy. Diet is also studied to determine its role in the aging process, and the effects of aging on memory. Further, brain cells and other components of the nervous system in aging are also being investigated at these centers. © 1994 Wiley-Liss, Inc., (Copyright © 1994 Wiley‐Liss, Inc., A Wiley Company.)

Enlargement of an accessory spleen following splenectomy may be due to compensatory hypertrophy or recurrence of hematologic or other disorders. Spontaneous necrosis and hemorrhage in an accessory spleen are rarely described. We report a case in which an enlarged accessory spleen complicated by spontaneous hemorrhage was identified on computed tomography (CT) and confirmed at surgery.

Nonhuman primates demonstrate marked similarities to humans in almost all aspects of their anatomy, endocrinology, and physiology. These similarities underlie the value of these animals for appropriate studies in neurobiology, immunology, pathology, reproductive biology, teratology, neonatology, endocrinology, cardiology, and psychology. Investigations with nonhuman primates has made, and continues to make, significant contributions to biomedical and behavioral research. This review provides an overview of basic and applied studies for which primates are appropriate subjects and a summary of the advantages and problems of using nonhuman primates in research.