Primary pancreatic lymphoma – pancreatic tumours that are potentially curable without resection, a retrospective review of four cases

BACKGROUND: Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. METHODS: Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. RESULTS: All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. CONCLUSION: Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes

Khat Use Is Associated with Impaired Working Memory and Cognitive Flexibility

Rationale Khat consumption has increased during the last decades in Eastern Africa and has become a global phenomenon spreading to ethnic communities in the rest of the world, such as The Netherlands, United Kingdom, Canada, and the United States. Very little is known, however, about the relation between khat use and cognitive control functions in khat users. Objective We studied whether khat use is associated with changes in working memory (WM) and cognitive flexibility, two central cognitive control functions. Methods Khat users and khat-free controls were matched in terms of sex, ethnicity, age, alcohol and cannabis consumption, and IQ (Raven's progressive matrices). Groups were tested on cognitive flexibility, as measured by a Global-Local task, and on WM using an N-back task. Result Khat users performed significantly worse than controls on tasks tapping into cognitive flexibility as well as monitoring of information in WM. Conclusions The present findings suggest that khat use impairs both cognitive flexibility and the updating of information in WM. The inability to monitor information in WM and to adjust behavior rapidly and flexibly may have repercussions for daily life activities

Estimating food production in an urban landscape

There is increasing interest in urban food production for reasons of food security, environmental sustainability, social and health benefits. In developed nations urban food growing is largely informal and localised, in gardens, allotments and public spaces, but we know little about the magnitude of this production. Here we couple own-grown crop yield data with garden and allotment areal surveys and urban fruit tree occurrence to provide one of the first estimates for current and potential food production in a UK urban setting. Current production is estimated to be sufficient to supply the urban population with fruit and vegetables for about 30 days per year, while the most optimistic model results suggest that existing land cultivated for food could supply over half of the annual demand. Our findings provide a baseline for current production whilst highlighting the potential for change under the scaling up of cultivation on existing land

The Detectability of Earth's Biosignatures Across Time

Over the past two decades, enormous advances in the detection of exoplanets have taken place. Currently, we have discovered hundreds of earth-sized planets, several of them within the habitable zone of their star. In the coming years, the efforts will concentrate in the characterization of these planets and their atmospheres to try to detect the presence of biosignatures. However, even if we discovered a second Earth, it is very unlikely that it would present a stage of evolution similar to the present-day Earth. Our planet has been far from static since its formation about 4.5 Ga ago; on the contrary, during this time, it has undergone multiple changes in it's atmospheric composition, it's temperature structure, it's continental distribution, and even changes in the forms of life that inhabit it. All these changes have affected the global properties of Earth as seen from an astronomical distance. Thus, it is of interest not only to characterize the observables of the Earth as it is today, but also at different epochs. Here we review the detectability of the Earth's globally-averaged properties over time. This includes atmospheric composition and biosignatures, and surface properties that can be interpreted as sings of habitability (bioclues). The resulting picture is that truly unambiguous biosignatures are only detectable for about 1/4 of the Earth's history. The rest of the time we rely on detectable bioclues that can only establish an statistical likelihood for the presence of life on a given planet.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018). arXiv admin note: text overlap with arXiv:astro-ph/0609398 by other author

Post hoc Analysis for Detecting Individual Rare Variant Risk Associations Using Probit Regression Bayesian Variable Selection Methods in Case-Control Sequencing Studies.

Rare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single-marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden-type approaches attempt to identify aggregation of RVs across case-control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large-scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway-level RV analysis results from a prostate cancer (PC) risk case-control sequencing study. Finally, we discuss potential extensions and future directions of this work

Hepatic arterial chemotherapy for primary and metastatic liver cancers

Hepatic arterial chemotherapy represents a means of selectively exposing hepatic tumor to cytotoxic agents. Although 5-fluoro-2′-deoxyuridine has been shown to generate a higher response rate in the treatment of colorectal liver metastases than that achieved by intravenous infusion, responses are largely incomplete and rarely of long duration. This review describes the rationale for the use of the thymidine analogs 5-bromo-2′-deoxyuridine and 5-iodo-2′-deoxyuridine in hepatic arterial infusions and indicates how combination therapy adding radiotherapy, specifically with hepatic arterially administered yttrium-90 microspheres, might generate a new, more efficient and effective therapeutic approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46919/1/280_2004_Article_BF00647244.pd

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury