The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Primary Liver Cancer Incidence Among American Indians and Alaska Natives, US, 1999–2004

BACKGROUND. American Indians and Alaska Natives (AI/AN) experience higher morbidity and mortality from primary liver cancer than other United States (US) populations, but racial misclassification in medical records results in underestimates of disease burden. METHODS. To reduce misclassification, National Program of Cancer Registries and Surveillance, Epidemiology, and End Results data were linked with Indian Health Service (IHS) enrollment records to compare primary liver cancer incidence and stage at diagnosis between AI/AN and non-Hispanic whites (NHW) living within the regionalized IHS Contract Health Service Delivery Area counties. Incidence rates are expressed per 100,000 persons and age-adjusted by 19 age groups to the 2000 US standard population. RESULTS. Overall, AI/AN have a higher proportion of hepatocellular carcinoma compared with NHW, 77.8% versus 66.7%. Liver cancer incidence rates among AI/ANmales and females were higher than those among NHW males and females for all regions except for the East. Among males, rates ranged from 7.3 (95% confidence interval [CI], 3.8-12.6) in the East to 17.2 (95% CI, 10.4-26.3) in Alaska. Among females, rates ranged from 3.8 (95% CI, 1.4-8.2) in the East to 6.9 (95% CI, 3.6-11.6) in Alaska. The AI/AN rates for all regions were consistently higher than the NHW rates at every age. An increasing trend among AI/AN was suggested but did not achieve statistical significance. CONCLUSIONS. Reducing racial misclassification revealed higher disparities in primary liver cancer incidence between NHW and AI/AN populations than previously reported. Further description of the reasons for regional differences in this disparity is needed, as are programs to reduce risk factors and to diagnose primary liver cancer at earlier, more treatable stages

Judicious Use of Lipid Lowering Agents in the Management of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD

The Role of Vitamin E in the Treatment of NAFLD

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect

When to Initiate Weight Loss Medications in the NAFLD Population

Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression

Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD

Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with “AND (NAFLD or NASH)”. Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb–drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread use can be recommended

National Trends and Disparities in the Incidence of Hepatocellular Carcinoma, 1998–2003

Introduction Previous studies indicate that the incidence of hepatocellular carcinoma in the United States is increasing. These reports, however, have contained limited information on population groups other than whites and blacks.MethodsWe assessed recent incidence rates and trends for hepatocellular carcinoma by using newly available national data from cancer registries participating in the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Data from registries in 38 states and the District of Columbia met our criteria; these data covered 83% of the U.S. population. We computed age-adjusted incidence rates and annual percentages of change from 1998 through 2003.ResultsThe registries that we used reported 48,048 cases of hepatocellular carcinoma (3.4 cases per 100,000 population per year) for the study period. Whites accounted for three-fourths of cases. The incidence rate for blacks was 1.7 times higher than that for whites, and the rate for Asians/Pacific Islanders was 4 times higher than that for whites. Hispanics had 2.5 times the risk of non-Hispanics. Among Asian/Pacific Islander subgroups, rates were highest for people of Vietnamese and Korean origin. For all races/ethnicities combined, the annual percentages of change were 4.8% for males and 4.3% for females (P < .05). The annual percentage of change was highest for people aged 45–59 years (9.0%, P < .05). The annual percentage of change for Asians/Pacific Islanders was statistically unchanged.ConclusionWe document rising incidence rates of hepatocellular carcinoma in the United States during a time when the overall incidence of cancer has stabilized. Efforts to collect representative etiologic data on new hepatocellular carcinoma cases are needed to enable better characterization of trends and to guide the planning and evaluation of prevention programs

Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited