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Since the start of COVID-19 pandemic, the definition of normal life has changed drastically. The number of cases of this pandemic is rising everyday across the globe. In this study, we propose a compartmental model, which considers the isolation factor of Coronavirus infected individuals. The model consists of five compartments: susceptible (S), exposed (E), Infected (I), Isolated (L) and recovered (R). We have estimated the parameters of the model system and the expression of the basic reproduction number \begin{document}$ R_0 $\end{document} using real data set. The exact value of the basic reproduction number is computed for India, Brazil and Peru. The local and global stability analysis of disease-free equilibrium and endemic equilibrium points is carried out. The forecasting of the pandemic is done using real data. It has been observed that to understand the pandemic the time frame has to be divided into small intervals as the parameters of the pandemic are changing with time. Within a time frame of approximately four months (i.e. from July to October 2020), the transmission rate of India has been reduced by approximately 84%. Whereas the transmission rate in Brazil and Peru has increased by 79% and 45% respectively. The sensitivity of various parameters involved in the model has been analyzed. We have presented a complete analysis to check the existence of backward bifurcation.

A major challenge for online and data-driven model learning in robotics is the high sample-complexity. This hinders its efficiency and practical feasibility for lifelong learning, in particular for developmental robots that autonomously bootstrap their sensorimotor skills in an open-ended environment. In this work, we propose new methods to mediate this problem in order to permit the learning of robot models online, from scratch, and in a learning while behaving fashion. Exploration is utilized and autonomously driven by a novel intrinsic motivation signal which combines knowledge-based and competence-based elements and surpasses other state-of-art methods. In addition, we propose an Episodic Online Mental Replay to accelerate the online learning, to ensure the sample-efficiency, and to update the model online rapidly. The efficiency as well as the applicability of our methods are demonstrated with a physical 7-DoF Baxter manipulator. We show that our learning schemes are able to drastically reduce the sample complexity and learn the data-driven model online, even within a limited time frame.

The way we currently capture biological processes in space and time often limits our understanding of plant development and stress responses, leading to an incomplete picture of plant life. Choosing the correct time frame for the study of every biological process, from seed germination to senescence or in plant stress responses, is essential, despite methodological limitations. A greater effort is needed in current plant biology studies to incorporate spatiotemporal approaches so that scientific knowledge meets the possibilities technological advances currently provide. From molecular, biochemical, and cellular approaches to (eco)physiological and population studies scaled up to the ecosystem level, there is an urgent need to link space and time using integrative and scalable data.

Objective To determine the incidence, characteristics (including timeframe) and predictors of patients discharged from the Emergency Department (ED) that later return and require admission. Methods A retrospective cross-sectional study examining all return visits to three EDs in Sydney, Australia, over a 12-month period. Patients returning within 28 days from ED discharge with the same or similar complaint were classified as a return visit to ensure capture of all return visits. Descriptive and inferential statistics were used to analyse the data and logistic regression was performed to predict factors associated with return visits with general admission, and return visits admitted to critical care. Results There were 1,798 (30%) return visits which resulted in admission, mostly to a non-critical care area (1,679, 93%). The current NSW 48 -h time frame used to define a return visit in NSW captured half of all admitted returns (49.5%) and just over half (59.2%) of critical care admissions. Variables associated with an admission to critical care were age (OR 1.02, 95% CI 1.01, 1.03), initial presentation (index visit) made to a lower level ED (OR 3.76 95% CI 2.06, 6.86), Triage Category 2 (OR 3.67 95% CI 2.04, 6.60) and a cardiac diagnosis (OR 5.76, 95% CI 3.01, 11.01). This model had adequate discriminant ability with AUROC = 0.825. Conclusion A small number of return visits result in admission, especially to critical care. These patients are at risk of poor outcomes. As such, clinicians should have increased index of suspicion for patients who return that are older, present with cardiac problems, or have previously presented to a lower level ED. Revision of the current timeframe that defines a return visit ought to be considered by policy makers to improve the accuracy of this widely used key performance indicator.

As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.

Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.

To compare the long-term results of Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK) in fellow eyes for treatment of Fuchs endothelial corneal dystrophy.This study is a 2-centered, retrospective case series of 64 patients (128 eyes) with DSAEK followed by DMEK. The main outcomes measured were best spectacle-corrected visual acuity (BSCVA) and duration of time to achieve BSCVA as well as eye preference.Preoperative median logarithm of the minimum angle of resolution (logMAR) BSCVA was similar in eyes receiving DMEK 0.36 ± 0.26 and DSAEK 0.42 ± 0.34 (P = .266). The average follow-up time needed for the DMEK eyes to achieve BSCVA was faster than that of DSAEK (277 days vs 490 days, P = .0014). With long-term follow-up, the BSCVA of the DMEK eyes [0.09 ± 0.10 logMAR] and DSAEK eyes [0.11 ± 0.16 logMAR] did not show a statistically significant difference (P = .069). Twenty-two of the 64 preferred the DMEK eye, 17 patients preferred the DSAEK eye (P = .423), and 25 patients did not have a preference. In the DMEK group, the average spherical equivalent was -0.08 compared with the DSAEK group at 0.06 (P = .2854).In our fellow eye study with long-term follow-up, DMEK and DSAEK had comparable levels of BSCVA and patient satisfaction. The DMEK eyes reached their BSCVA sooner, whereas the DSAEK eyes improved over a longer time frame. A greater number of patients had 20/25 and 20/20 vision in the DMEK group; however, the difference was not statistically significant. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Highlights • The MR-Linac provides the tools to deliver online MR-guided Adaptive Radiotherapy • Adapt-to-Shape-Lite is a novel radiotherapy planning workflow on the Elekta Unity MR-Linac • Adapt-to-Shape-Lite generated plans that fulfilled 99.9% of mandatory dose constraints • Adapt-to-Shape-Lite workflow can generate plans in relatively short durations • Therefore, we prefer Adapt-To-Shape-Lite as the primary workflow to treat Head-and-Neck cancers, Introduction The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). Methods Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. Results 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s – 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s – 44 mins 27 s), respectively. Conclusions Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL.

The bachelor thesis discusses the time frame of the work of general nurses in a standard workplace. The theoretical part describes information about the practice of the profession and education in the field of general nursing (conditions for the practice of the profession, qualification, specialization and lifelong education). Furthermore, the specifics of the profession of a general nurse are described, including competencies, the nursing care provided by general nurses is defined, and the documentation of health service providers, which is maintained by general nurses, is also presented. The next part of the bachelor's thesis deals with the analysis of work in nursing, presents its methodology (time frame of the working day, observation, interview), which will be used for the development of the research part of the work. The tools used to measure the workload of general nurses in a standard workplace are also compared with the same tools used in intensive care units. The aim of the bachelor's thesis is to find out what activities a general nurse performs during a shift, including the time-consuming nature of these activities, and the subsequent mapping of work optimization topics proposed by observed general nurses at a standard workplace. The research part is implemented using a qualitative research method, where the research sample consists of general nurses from a selected standard workplace. Using a semi-structured observation of a time frame of the work of general nurses, time data is collected about the time used for individual activities performed. Through a semi-structured interview, general nurses' suggestions for optimizing work at a standard workplace in terms of time are ascertained.

60+ years of planning for a human mission to Mars are documented, based on Portree’s superb history. Starting with von Braun’s vision of the 1950s, many attempts were made to define a feasible human mission to Mars. Development of nuclear thermal propulsion (NTP) began in the 1950s and 1960s. In 1968, Boeing published a detailed design of a human mission to Mars making extensive use of NTP. The Boeing 1968 study set a high bar for extraordinary detail in analysis of the many subsystems and components needed for a human mission to Mars. It is unfortunate that many subsequent studies failed to come close to clearing that bar. Mission concepts continued to appear through the 1970s and 1980s. In the 1990s, NASA produced Design Reference Missions DRM-1 and DRM-3 that became standard bearers for Mars planning. These DRMs introduced important use of ISRU, and continued to rely on NTP. In the same time frame, Zubrin developed the Mars Direct concept and Caltech developed the Mars Society Mission concept. In 2005, NASA published a summary of an extensive mission study known as DRA-5, but backup for this summary does not seem to be available. In 2014, NASA announced the Evolvable Mars Campaign. It seems likely that the EMC is just another NASA boondoggle using vague and ephemeral notions based on glossy viewgraphs, and a total lack of detailed engineering calculations. It will end up being scrapped for good reasons, as NASA moves on to its next long-range plan. After 60+ years of planning, we still don’t have a plan.

O artigo apresenta um levantamento bibliográfico acerca do tema “violência na escola pública”. Refere-se a um estudo que se sustenta na análise de 16 dissertações e teses depositadas na Biblioteca Digital de Teses e Dissertações (BDTD). Utilizou-se como marco temporal o período de 2012 a 2019, creditando a produção acadêmica mais atual sobre o tema. No desenvolvimento da análise, considerou-se, principalmente, os objetivos dos estudos, algumas compreensões acerca da temática textualizadas nas pesquisas e as metodologias utilizadas. Concluiu-se que o tema “violência na escola pública” é complexo. Sua compreensão textualizada nas produções acadêmicas necessita estar associada às questões de cunho social mais amplo. No entanto, identificou-se que a escola pública tem condições de minimizar os diferentes tipos de violência que se sucedem em seu interior. Para isso, é essencial o trabalho coletivo e dialógico produzido em seu cotidiano.

Este artigo apresenta resultados de uma investigação bibliográfica acerca de como a avaliação educacional é contemplada nos Projetos Pedagógicos de Cursos – PPCs de licenciaturas. O estudo caracteriza-se como uma pesquisa qualitativa, na perspectiva do Estado do Conhecimento. O recorte temporal compreende os anos entre 2009 a 2019, sendo o material bibliográfico coletado nas seguintes bases de dados: Biblioteca Digital de Teses e Dissertações (BDTD); Catálogo de Teses e Dissertações da CAPES; bibliotecas online de programas de pós-graduação em avaliação (educacional); Google e Scientific Electronic Library Online (SciELO). Os resultados encontrados nos trabalhos inventariados revelam que a avaliação educacional aparece de forma pontual nos documentos de curso, como disciplina ou na ementa de outras disciplinas, mas não recebe atenção de forma aprofundada, enquanto transdisciplina. Destaca-se o abismo entre estar presente no PPC versus a prática de avaliação de docentes, pois não fica claro se estas são pautadas apenas na avaliação para verificação da aprendizagem ou na avaliação para promoção das aprendizagens.

Nowadays, thermal conductivity as a key parameter affecting the thermal performance of PCM has attracted much attention. However, the thermal performance evaluation of ultra-high thermal conductivity PCM is scarce, especially in field of building energy conservation. Therefore, we traversed the range of thermal conductivity that can be prepared at present and within the expected time frame, which is 0.08–49.28 W ⋅ m − 1 K − 1 . In addition, a novel index, Utilization Rate of Latent Heat (URLH), was proposed to evaluate matching degree between PCM and a certain application background in buildings, so as to explore the reason of poor energy-saving effect of PCM under some application backgrounds. We found that the thermal conductivity of PCM is not the higher the better in buildings, in other words, a turning point appears. The optimal thermal conductivity is about 0.6 W ⋅ m − 1 K − 1 and when the value is lower than 0.3 W ⋅ m − 1 K − 1 , URLH is equal to 0 in the cases of Shanghai. Therefore, we recommend PCM researchers to evaluate the URLH before using PCM to avoid the ineffective use of materials. Through the analysis of URLH, researchers can know the specific parameters that affect the thermal performance of PCM and obtain the way to optimize them.

Objective To describe the experience of COVID-19 disease among chronically ventilated and nonventilated nursing home patients living in 3 separate nursing homes. Design Observational study of death, respiratory illness and COVID-19 polymerase chain reaction (PCR) results among residents and staff during nursing home outbreaks in 2020. Setting and Participants 93 chronically ventilated nursing home patients and 1151 nonventilated patients living among 3 separate nursing homes on Long Island, New York, as of March 15, 2020. Illness, PCR results, and antibody studies among staff are also reported. Measurements Data were collected on death rate among chronically ventilated and nonventilated patients between March 15 and May 15, 2020, compared to the same time in 2019; prevalence of PCR positivity among ventilated and nonventilated patients in 2020; reported illness, PCR positivity, and antibody among staff. Results Total numbers of deaths among chronically ventilated nursing home patients during this time frame were similar to the analogous period 1 year earlier (9 of 93 in 2020 vs 8 of 100 in 2019, P = .8), whereas deaths among nonventilated patients were greatly increased (214 of 1151 in 2020 vs 55 of 1189 in 2019, P < .001). No ventilated patient deaths were clinically judged to be COVID-19 related. No clusters of COVID-19 illness could be demonstrated among ventilated patients. Surveillance PCR testing of ventilator patients failed to reveal COVID-19 positivity (none of 84 ventilator patients vs 81 of 971 nonventilator patients, P < .002). Illness and evidence of COVID-19 infection was demonstrated among staff working both in nonventilator and in ventilator units. Conclusions and Implications COVID-19 infection resulted in illness and death among nonventilated nursing home residents as well as among staff. This was not observed among chronically ventilated patients. The mechanics of chronic ventilation appears to protect chronically ventilated patients from COVID-19 disease.

The urgent need to fight the COVID-19 pandemic has impressively stimulated the efforts of the international scientific community, providing an extraordinary wealth of studies. After the sequence of the virus became available in early January 2020, safe and effective vaccines were developed in a time frame much shorter than everybody expected. However, additional studies are required since viral mutations have the potential of facilitating viral transmission, thus reducing the efficacy of developed vaccines. Therefore, improving the current laboratory testing methods and developing new rapid and reliable diagnostic approaches might be useful in managing contact tracing in the fight against both the original SARS-CoV-2 strain and the new, potentially fast-spreading CoV-2 variants. Mass Spectrometry (MS)-based testing methods are being explored, with the challenging promise to overcome the many limitations arising from currently used laboratory testing assays. More specifically, MALDI-MS, since its advent in the mid 1980s, has demonstrated without any doubt the great potential to overcome many unresolved analytical challenges, becoming an effective proteomic tool in several applications, including pathogen identification. With the aim of highlighting the challenges and opportunities that derive from MALDI-based approaches for the detection of SARS-CoV-2 and its variants, we extensively examined the most promising proofs of concept for MALDI studies related to the COVID-19 outbreak.

This paper aimed to list the natural and social conditions that may have guided the dawn of some cities in the Far Northwest of Sao Paulo during the 20th century. Therefore, a case study was made on the urban history of Santa Fe do Sul and Rubineia (SP) to relate the occupation and formation of cities with elements of landscape and society. The time frame that begins in the 19th century with the eviction of natives by the people of Minas Gerais, discusses the strategies of the coffee economy and the close relationship with railroads, culminating in the formation of both cities in mid-20th century. For this purpose, it was necessary a literature review regarding the occupation of the hinterland of Sao Paulo and the local urban history, besides a documental research in primary sources that discussed the urban spaces. The research develops qualitatively and analyzes, empirically, the initial morphology of the referred cities. The influence of the streams delimitating rural properties and how these bodies of water directed the railway was found, discovery that in turn guided the urban layout of the cities analyzed. About the social factors, it was found that Porto Taboado, Estrada de Ferro Araraquara and the socioeconomic context of the time were of great importance on forming and definition of the cities in the region. Finally, from the study of both cities, this paper discussed the historical processes that formed them and may serve as an aid for studies of urban history in the municipalities located in the same context.

Photochemistry is an important topic which is relevant regarding the usage of solar light as clean energy source. By employing photoreactions, a broad variety of molecular transformations can be conducted which is different from classical thermal chemistry. Ketones provide advantages and thus can be used as model compounds to develop central aspects and principles of photochemistry for teaching purposes. A photochemical experiment for university teaching, dealing with the basic reaction modes of ketones with γ-C-H-bonds, can be introduced and adjusted to the learners capability and pre-knowledge. Different basic characteristics of photochemistry and radical reactions as well as advanced topics and working techniques can be accessed in a hands-on-way using the model reaction. Depending on the equipment and the time frame available, the experiment can be conducted on preparative or on micro scale.

Cervical cancer is a major source of morbidity and mortality in Uganda. In addition to prophylactic HPV vaccination, secondary prevention strategies are needed to reduce cancer burden. We evaluated the potential cancer reductions associated with a hypothetical single-contact therapeutic HPV intervention-with 70% coverage and variable efficacy [30%-100%]-using a three-stage HPV modeling framework reflecting HPV and cervical cancer burden in Uganda. In the reference case, we assumed prophylactic preadolescent HPV vaccination starting in 2020 with 70% coverage. A one-time therapeutic intervention targeting 35-year-old women in 2025 (not age-eligible for prophylactic vaccination) averted 1801 cervical cancers per 100 000 women over their lifetime (100% efficacy) or 533 cancers per 100 000 (30% efficacy). Benefits were considerably smaller in birth cohorts eligible for prophylactic HPV vaccination (768 cases averted per 100 000 at 100% efficacy). Evaluating the population-level impact over 40 years, we found introduction of a therapeutic intervention in 2025 with 100% efficacy targeted annually to 30-year-old women averted 139 000 incident cervical cancers in Uganda. This benefit was greatly reduced if efficacy was lower (30% efficacy; 41 000 cases averted), introduction was delayed (2040 introduction; 72 000 cases averted) or both (22 000 cases averted). We demonstrate the potential benefits of a single-contact HPV therapeutic intervention in a low-income setting, but show the importance of high therapeutic efficacy and early introduction timing relative to existing prophylactic programs. Reduced benefits from a less efficacious intervention may be somewhat offset if available within a shorter time frame.

BackgroundCT performed within 6 hours of headache onset is highly sensitive for the detection of subarachnoid haemorrhage (SAH). Beyond this time frame, if the CT is negative for blood, a lumbar puncture is often performed. Technology improvements in image noise reduction, resolution and motion artefact have enhanced the performance of multislice CT (MSCT) and may have further improved sensitivity. We aimed to describe how the sensitivity to SAH of modern MSCT changes with time from headache onset.MethodsThis was a retrospective analysis of electronic data collected as part of routine care among all patients presenting to Christchurch Hospital diagnosed with a SAH between 1 January 2008 and 31 December 2017. Patients were imaged with MSCT. The primary outcome was the proportion of patients with spontaneous aneurysmal SAH (identified via coding and confirmed by clinical and radiological records) that had a positive MSCT. The secondary outcome was the proportion of patients with any type of spontaneous SAH that had a positive MSCT.ResultsThere were 347 patients with an SAH of whom 260 were aneurysmal SAH. MSCT identified 253 (97.3%) of all aneurysmal SAH and 332 (95.7%) of all SAH. The sensitivity of MSCT was 99.6% (95% CI 97.6 to 100) for aneurysmal SAH and 99.0% (95% CI 97.1 to 99.8) for all SAH at 48 hours after headache onset. At 24 hours after headache onset, the sensitivity for aneurysmal SAH was 100% (95% CI 98.3 to 100).ConclusionThese data suggest that it may be possible to extend the timeframe from headache onset within which modern MSCT can be used to rule out aneurysmal SAH.

Este artigo apresenta os resultados de uma pesquisa do tipo Estado do Conhecimento, realizada com o objetivo de mapear e analisar as produções científicas sobre o coordenador pedagógico no Brasil. Os textos analisados são teses localizadas na Biblioteca Digital Brasileira de Teses e Dissertações (BDTD/Ibict) e no Catálogo de Teses e Dissertações da Coordenadoria de Aperfeiçoamento de Professores do Ensino Superior (CTD/CAPES). Para acessar os textos utilizamos a ferramenta eletrônica de busca com as palavras-chave “coordenador pedagógico” e “coordenação pedagógica”, tendo como filtro o recorte temporal de 2009 a 2019. Foram localizados 255 teses, das quais foram selecionadas 25 para análise dos resumos – somente aquelas que tinham como foco a atuação do coordenador pedagógico nas etapas do Ensino Fundamental e Ensino Médio da Educação Básica. As análises apontam que a maior parte das teses encontradas para as palavras-chave “coordenador pedagógico” e “coordenação pedagógica” enfatizam o seu processo formativo. Quanto a temática “bem-estar dos coordenadores pedagógicos”, concluímos que é uma temática ainda não discutida na academia, pois não foi localizado nenhum trabalho sobre o tema. Entendemos, por meio deste Estado do Conhecimento, ter encontrado um campo propício a novas pesquisas.

Introduction: Despite advances in the understanding of the molecular pathogenesis of cutaneous melanoma, relatively little is known about the genetic changes that occur in the progression of conjunctival melanocytic intraepithelial lesions to invasive conjunctival melanoma. Methods: We exposed 4 exenteration specimens that each contained varying grades of intraepithelial conjunctival melanocytic neoplasia and invasive neoplasia to a combination of various techniques, including array comparative genomic hybridization (aCGH), ribonucleic acid sequencing (RNA-seq), fluorescence in situ hybridization (FISH), and immunohistochemistry. Results: Three out of 4 of the invasive melanomas showed gains in 11q13 (CCND1 locus) by aCGH. FISH demonstrated CCND1 gain in invasive melanoma and in conjunctival melanocytic intraepithelial lesions (CMILs) of all grades (low-grade CMILs and in situ melanoma), and this was paralleled by increased expression of Cyclin D1 protein within the atypical melanocytes by immunohistochemistry, using a double-staining method with a red end point for Melan A cytoplasmic staining and a brown end point for nuclear Cyclin D1 expression. Higher grades of melanocytic intraepithelial lesions showed more cells expressing Cyclin D1 than lower grade melanocytic intraepithelial lesions. The Cyclin D1 protein expression was in the same location as the amplified CCND1 signal by FISH. One out of 3 of these cases also showed the amplification of the 12q13-15 locus corresponding to MDM2 and FISH confirmed gains in the conjunctival melanocytic intraepithelial neoplasia and invasive melanoma. The remaining fourth case showed a homozygous deletion of 9p21 (CDKN2A) by aCGH only, with immunohistochemistry showing clonal loss of p16 protein expression in the invasive and conjunctival melanocytic intraepithelial lesion. Two out of 4 of the invasive melanomas harboured classical driver mutations in NRAS and NF-1, respectively. None of the cases showed mutations in BRAF, KIT, and TERT mutations. RNA-seq data showed secondary mutations in ARAF, PLCB4, MET, EZH2, MAP2K2, CTNNB1, CIITA, NF2, TP53, and MEN1, some of which are implicated in the MAPK pathway. Conclusion: CMILs harbour amplifications of CCND1 (3 cases), MDM2 (1 case), and loss of CDKN2A (1 case), which are also present when the lesion progresses to invasive melanoma, implicating these amplifications in the early pathogenesis of CMILs. This study represents the first attempt to capture the mutational landscape of all stages of conjunctival melanoma in a single tissue excision.

A large debate has risen about the hypothesis that “COVID-19 is a disease for the rich ones” suggesting that both its diffusion and mortality rates are somehow linked with economic wealth. In this study we observe a sample of 138 countries during the first wave contagion period, namely the 5 weeks between 24 March and 21 April 2020. Using different data sources, our estimates show that both the early infection and the mortality rates of COVID-19 are higher in wealthier countries, more precisely in countries with a higher GDP per capita. As an explanation of this finding, we also find that both mortality and infection rates increase with a higher share of elderly population and with the international flows of imported goods or tourists. However, the death rate decreases in countries with higher endowments of health facilities. We also demonstrate that these results are robust to simultaneity, unobserved heterogeneity, the possible poor quality of the data on COVID-19 deaths, and the extension of the time frame.

The emergence of big data has caused various challenges to data management lifecycle including storage, processing, sharing, and applications. During the same time frame, the fast development in cloud computing provides increased efficiency in computing support that address these challenges. However, there are issues in big data and cloud computing management which include security concerns, data fragmented, and distrust in using clouds that could become the roadblock to e-government services success. Although ensuring data management has been the responsibility of providers in the public sector, this issue seems to be unavoidable. In such circumstances, initiatives from the public sector agencies are crucial to ensure data is effectively managed. This research in progress aims to investigate how the public sector agencies in Terengganu manage data to improve the e-government performance. The research uses the interpretive research paradigm and adopts the qualitative research methodology using a case study design. A single case of a public sector which utilizes big data and cloud computing within the e-government platform is selected as the case for this research. The findings of this research are expected to be used in developing a framework of big data and cloud computing management which will assist in providing reliable and accurate information to citizens within the e-government environment.