Immigration and Naturalization

Immigration law has always been interesting and controversial. Yet in 2018, it became disproportionately so. Law and policymakers identified issues such as unlawful migration, the border between the United States and Mexico, Muslim immigration, and even high-skilled worker visas as critical election issues in anticipation of the 2018 midterm election. Additionally, the current U.S. Executive Branch has taken a hardline approach to immigration, pursuing opportunities to limit, rather than expand, access by non-citizens to U.S. opportunities. As a prime policy example, the fact that U.S. Citizenship and Immigration Services (USCIS), that is responsible for processing immigration and naturalization applications and establishing policies regarding immigration services, changed its mission statement from America\u27s promise as a nation of immigrants to protecting Americans, securing the homeland, and honoring our values gives us a perspective of the scope of the transformation. From the Trump-era immigration policy changes that include family separations, to indefinite detention with no right to bond hearings, to the horrors of denying asylum to victims of domestic violence, to forcefully outing same sex partners of diplomats, we will review some of the new American immigration reality

Accurate measurement of 5-methylcytosine and 5-hydroxymethylcytosine in human cerebellum DNA by oxidative bisulfite on an array (OxBS-array).

The Infinium 450K Methylation array is an established tool for measuring methylation. However, the bisulfite (BS) reaction commonly used with the 450K array cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The oxidative-bisulfite assay disambiguates 5mC and 5hmC. We describe the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA. The "methylation" level derived by the BS reaction is the combined level of 5mC and 5hmC at a given base, while the oxBS reaction gives the level of 5mC alone. The level of 5hmC is derived by subtracting the oxBS level from the BS level. Here we present an analysis method that distinguishes genuine positive levels of 5hmC at levels as low as 3%. We performed four replicates of the same sample of cerebellum and found a high level of reproducibility (average r for BS = 98.3, and average r for oxBS = 96.8). In total, 114,734 probes showed a significant positive measurement for 5hmC. The range at which we were able to distinguish 5hmC occupancy was between 3% and 42%. In order to investigate the effects of multiple replicates on 5hmC detection we also simulated fewer replicates and found that decreasing the number of replicates to two reduced the number of positive probes identified by > 50%. We validated our results using qPCR in conjunction with glucosylation of 5hmC sites followed by MspI digestion and we found good concordance with the array estimates (r = 0.94). This experiment provides a map of 5hmC in the cerebellum and a robust dataset for use as a standard in future 5hmC analyses. We also provide a novel method for validating the presence of 5hmC at low levels, and highlight some of the pitfalls associated with measuring 5hmC and 5mC.S. Balasubramanian is a Senior Investigator of The Wellcome Trust and the Balasubramanian group is core-funded by Cancer Research UK. We would like to thank Tobias Ost and Christine Clark of Cambridge Epigenetix Ltd. for valuable discussions and development of the method.This article was originally published in PLOS ONE (Field SF, Beraldi D, Bachman M, Stewart SK, Beck S, Balasubramanian S, PLoS ONE 2015, 10(2): e0118202. doi:10.1371/journal.pone.0118202

Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea similar to 0.46 million years ago (mya) and equatorial Africa similar to 0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until similar to 0.10-0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon population

Risk Prediction Models for Kidney Cancer: A Systematic Review

Context Early detection of kidney cancer improves survival; however, low prevalence means that population-wide screening may be inefficient. Stratifying the population into risk categories could allow for the introduction of a screening program tailored to individuals. Objective This review will identify and compare published models that predict the risk of developing kidney cancer in the general population. Evidence Acquisition A search identified primary research reporting or validating models predicting the risk of kidney cancer in Medline and EMBASE. After screening identified studies for inclusion, we extracted data onto a standardised form. The risk models were classified using TRIPOD guidelines and evaluated using the PROBAST assessment tool. Evidence Synthesis The search identified 15,281 articles. Sixty-two satisfied the inclusion criteria; performance measures were provided for 11 models. Some models predicted the risk of prevalent undiagnosed disease and others future incident disease. Six of the models had been validated, two using external populations. The most commonly included risk factors were age, smoking status and BMI. Most of the models had acceptable-to-good discrimination (AUROC>0.7) in development and validation. Many also had high specificity; however, several had low sensitivity. The highest performance was seen for the models using only biomarkers to detect kidney cancer; however, these were developed and validated in small case-control studies. Conclusion We identified a small number of risk models that could be used to stratify the population according to risk of kidney cancer. Most exhibit reasonable discrimination but few have been externally validated in population-based studies. Patient Summary In this review, we looked at mathematical models predicting the likelihood of an individual developing kidney cancer. We found several suitable models, using a range of risk factors (such as age and smoking) to predict individual risk. Most of the models identified require further testing in the general population to confirm their usefulness.NIHR - RM-SR-2017-09-009 CRUK - C55650/A2146

The prevalence of multimorbidity in primary care: a comparison of two definitions of multimorbidity with two different lists of chronic conditions in Singapore

Background: The prevalence of multimorbidity varies widely due to the lack of consensus in defining multimorbidity. This study aimed to measure the prevalence of multimorbidity in a primary care setting using two definitions of multimorbidity with two different lists of chronic conditions. Methods: We conducted a cross-sectional study of 787,446 patients, aged 0 to 99 years, who consulted a family physician between July 2015 to June 2016. Multimorbidity was defined as ‘two or more’ (MM2+) or ‘three or more’ (MM3+) chronic conditions using the Fortin list and Chronic Disease Management Program (CDMP) list of chronic conditions. Crude and standardised prevalence rates were reported, and the corresponding age, sex or ethnic-stratified standardised prevalence rates were adjusted to the local population census. Results: The number of patients with multimorbidity increased with age. Age-sex-ethnicity standardised prevalence rates of multimorbidity using MM2+ and MM3+ for Fortin list (25.9, 17.2%) were higher than those for CDMP list (22.0%; 12.4%). Sex-stratified, age-ethnicity standardised prevalence rates for MM2+ and MM3+ were consistently higher in males compared to females for both lists. Chinese and Indians have the highest standardised prevalence rates among the four ethnicities using MM2+ and MM3+ respectively. Conclusions: MM3+ was better at identifying a smaller number of patients with multimorbidity requiring higher needs compared to MM2+. Using the Fortin list seemed more appropriate than the CDMP list because the chronic conditions in Fortin’s list were more commonly seen in primary care. A consistent definition of multimorbidity will help researchers and clinicians to understand the epidemiology of multimorbidity better

Public attitudes towards screening for kidney cancer: an online survey

Funder: Kidney Cancer UKFunder: The Urology FoundationAbstract: Background: Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme. Methods: We conducted an online population-based survey of 1021 adults aged 45–77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test. Results: Most participants stated that they would be ‘very likely’ or ‘likely’ to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43–0.73)] or ultrasound [OR 0.50 (0.38–0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14–0.27)]. Conclusion: Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes