The Rocky Road to a Digital Lab

The pharmaceutical industry has begun incorporating continuous manufacturing technology in synthetic routes toward active pharmaceutical ingredients (APIs). The development of smart manufacturing routes can be accelerated by utilizing digitalization, process analytical technology (PAT), and data-rich experimentation from an early stage. Here, we present the key aspects of implementing automated flow chemistry reactor platforms with real-time process analytics. Based on our experiences in this field, we aim to highlight the potential of these platforms to conduct self-optimization, automated reaction model building, dynamic experiments and to implement advanced process control strategie

Bumblebees of the Azores (Apidae: Bombus)

Bombus terrestris and Bombus pratorum were found for the first time in the Azores in 2005. Until then Bombus ruderatus was the only bumblebee species known from this group of nine midAtlantic islands. The identity of B. terrestris was confirmed by DNA barcoding

Using Mobile Phones to Improve Vaccination Uptake in 21 Low- and Middle-Income Countries: Systematic Review

Background: The benefits of vaccination have been comprehensively proven, however disparities in coverage persist due to poor health system management, limited resources and parental knowledge and attitudes. Evidence suggests that health interventions that engage local parties in communication strategies improve vaccination uptake. As mobile technology is widely used to improve health communication, mobile health (mHealth) interventions might be used to increase coverage. Objective: To conduct a systematic review of the available literature on the use of mHealth to improve vaccination in low and middle income countries with large numbers of unvaccinated children. Methods: In February 2017, MEDLINE, Scopus and Web of Science, and three health organization websites; Communication Initiative Network, TechNet-21, and PATH, were searched to identify mHealth intervention studies on vaccination uptake in 21 countries. Results: Ten peer-reviewed studies and eleven studies from white or grey literature were included. Nine took place in India, three in Pakistan, two each in Malawi and Nigeria, and one each in Bangladesh, Zambia, Zimbabwe and Kenya. Ten peer-reviewed studies and seven white/grey studies demonstrated improved vaccination uptake after interventions, including appointment reminders, mobile phone apps and pre-recorded messages. Conclusions: While the potential for mHealth interventions to improve vaccination coverage seems clear, the evidence for such interventions is not. The dearth of studies in countries facing the greatest barriers to immunization impedes the prospects for evidence-based policy and practice in these settings.The study was funded by the Medical Research Council, British Heart Foundation, and Homerton College, Cambridge

Rapid one-step biotinylation of biological and non-biological surfaces

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells

Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screening programme

Background This study aims to assess how the prevalence and growth rates of small and medium AAAs (3.0-5.4cm) have changed over time in men aged 65 years, and to evaluate long-term outcomes in those men whose aortic diameter is 2.6-2.9cm (subaneurysmal), and below the standard threshold for most surveillance programmes. Methods The Gloucestershire Aneurysm Screening Programme (GASP) started in 1990. Men aged 65 years with an aortic diameter of 2.6-5.4cm, as measured by ultrasound using the inner to inner wall method, were included in surveillance. Aortic diameter growth rates were estimated separately for men who initially had a subaneurysmal aorta, or who had a small or medium AAA, using mixed-effects models. Results Since 1990, 81,150 men had ultrasound screening for AAA (uptake 80.7%), of whom 2,795 had an aortic diameter of 2.6-5.4cm. The prevalence of screen-detected AAA ≥3.0cm decreased from 5.0% in 1991 to 1.3% in 2015. There was no evidence of a change in AAA growth rates during this time. Of men who initially had a subaneurysmal aorta, 58% (95% CI 54, 61) were estimated to develop an AAA ≥3.0cm within 5 years of their initial scan, and 28% (95% CI 24, 32) were estimated to develop a large AAA (≥5.5cm) within 15 years. Conclusions The prevalence of screen-detected small and medium AAA has decreased over the last 25 years, but growth rates have remained similar. Men with a subaneurysmal aorta at age 65 have a substantial risk of developing a large AAA by the age of 80 years.Before its adoption into the national programme, GASP was funded by Gloucestershire Hospitals NHS Foundation Trust. The present research was facilitated by a grant from the Gloucester Vascular Research Trust Fund

APM 08279+5255: an ultraluminous BAL quasar at a redshift z=3.87

We report on the discovery of a highly luminous, broad absorption line quasar at a redshift of $z=3.87$ which is positionally coincident, within one arcsecond, with the IRAS FSC source F08279+5255. A chance alignment of the quasar and the IRAS source is extremely unlikely and we argue that the optical and FIR flux are different manifestations of the same object. With an R-band magnitude of 15.2, and an IRAS 60\mum flux of 0.51\jy, APM 08279+5255 is (apparently) easily the most intrinsically luminous object known, with L_{Bol}\sim5\times10^{15}L_{\odot}}. Imaging suggests that gravitational lensing may play a role in amplifying the intrinsic properties of the system. The optical spectrum of the quasar clearly reveals the presence of three potential lensing galaxies, \mg absorption systems at $z=1.18$ and $z=1.81$, and a \ly absorption system at $z=3.07$. We estimate the total amplification of the optical component to be $\approx40$, but, due to the larger scale of the emitting region, would expect the infrared amplification to be significantly less. Even making the conservative assumption that all wavelengths are amplified by a factor 40, APM 08279+5255 still possesses a phenomenal luminosity of \simgt 10^{14L_{\odot}}, indicating that it belongs to a small, but significant population of high--redshift, hyperluminous objects with copious infrared emission.Comment: 15 Pages with Four figures. Accepted for publication in the Astrophysical Journa

The TRiC/CCT chaperone is implicated in Alzheimer's disease based on patient GWAS and an RNAi screen in Aβ-expressing Caenorhabditis elegans.

The human Aβ peptide causes progressive paralysis when expressed in the muscles of the nematode worm, C. elegans. We have exploited this model of Aβ toxicity by carrying out an RNAi screen to identify genes whose reduced expression modifies the severity of this locomotor phenotype. Our initial finding was that none of the human orthologues of these worm genes is identical with the genome-wide significant GWAS genes reported to date (the "white zone"); moreover there was no identity between worm screen hits and the longer list of GWAS genes which included those with borderline levels of significance (the "grey zone"). This indicates that Aβ toxicity should not be considered as equivalent to sporadic AD. To increase the sensitivity of our analysis, we then considered the physical interactors (+1 interactome) of the products of the genes in both the worm and the white+grey zone lists. When we consider these worm and GWAS gene lists we find that 4 of the 60 worm genes have a +1 interactome overlap that is larger than expected by chance. Two of these genes form a chaperonin complex, the third is closely associated with this complex and the fourth gene codes for actin, the major substrate of the same chaperonin

The Association between Parity and Subsequent Cardiovascular Disease in Women: The Atherosclerosis Risk in Communities Study

Background: Previous studies are inconclusive on the relationship between parity and cardiovascular disease (CVD), with few evaluating multiple cardiovascular outcomes. It is also unclear if any relationship between parity and CVD is independent of breastfeeding. We examined the associations between parity and cardiovascular outcomes, including breastfeeding adjustment. Materials and Methods: Data were from 8,583 White and African American women, 45-64 years of age, in the Atherosclerosis Risk in Communities Study. Coronary heart disease (CHD), myocardial infarction (MI), heart failure, and strokes were ascertained from 1987 to 2016 by annual interviews and hospital surveillance. Parity and breastfeeding were self-reported. Cox proportional hazards regression estimated hazard ratios (HR) for the association between parity and cardiovascular outcomes, adjusting for baseline sociodemographic, clinical and lifestyle factors, and breastfeeding. Results: Women reported no pregnancies (6.0%), or having 0 (1.6%), 1-2 (36.2%), 3-4 (36.4%), or 5+ (19.7%) live births. During 30 years follow-up, there were 1,352 CHDs, 843 MIs, 750 strokes, and 1,618 heart failure events. Compared with women with 1-2 prior births, those with prior pregnancies and no live births had greater incident CHD (HR=1.64, 95% confidence interval 1.14-2.42) and heart failure risk (1.46, 1.04-2.05), after adjustment for baseline characteristics. Women with 5+ births had greater risk of CHD (1.29, 1.10-1.52) and hospitalized MI (1.38, 1.13-1.69), after adjustment for baseline characteristics and breastfeeding. Conclusions: In a diverse U.S. cohort, a history of 5+ live births is associated with CHD risk, specifically, MI, independent of breastfeeding. Having a prior pregnancy and no live birth is associated with greater CHD and heart failure risk

Apparent Loss of Vibrio vulnificus from North Carolina Oysters Coincides with a Drought-Induced Increase in Salinity

ABSTRACT Despite years of successful isolation of Vibrio vulnificus from estuarine waters, beginning in 2007, it was extremely difficult to culture V. vulnificus from either North Carolina estuarine water or oyster samples. After employing culture-based methods as well as PCR and quantitative PCR for the detection of V. vulnificus , always with negative results, we concluded that this pathogen had become nearly undetectable in the North Carolina estuarine ecosystem. We ensured that the techniques were sound by seeding North Carolina oysters with V. vulnificus and performing the same tests as those previously conducted on unadulterated oysters. V. vulnificus was readily detected in the seeded oysters using both classes of methods. Furthermore, oysters were obtained from the Gulf of Mexico, and V. vulnificus was easily isolated, confirming that the methodology was sound but that the oysters and waters of North Carolina were lacking the V. vulnificus population studied for decades. Strikingly, the apparent loss of detectable V. vulnificus coincided with the most severe drought in the history of North Carolina. The drought continued until the end of 2009, with an elevated water column salinity being observed throughout this period and with V. vulnificus being nearly nonexistent. When salinities returned to normal after the drought abated in 2010, we were again able to routinely isolate V. vulnificus from the water column, although we were still unable to culture it from oysters. We suggest that the oysters were colonized with a more salt-tolerant bacterium during the drought, which displaced V. vulnificus and may be preventing recolonization

Refugees' views of the effectiveness of support provided by their host countries.

BACKGROUND: The war in former Yugoslavia, which commenced in 1990, caused the biggest refugee crisis in Europe since World War II. There are numerous research investigations into the trauma and associated problems. However, there is no available publication concerning refugees' own perception of the provided support in host countries. AIMS: To investigate how refugees evaluated support received (helpful or detrimental) and what kinds of support they wish to receive in the future. METHOD: The study participants were 854 refugees from former Yugoslavia settled in the United Kingdom, Germany, and Italy. Alongside demographic data, they were assessed using International Neuropsychiatric Interview (MINI), Life Stressor Checklist-Revised (LSC-R), Manchester Short Assessment of Quality of Life (MANSA), Matrix for Recording Health Care, Social Interventions (MACSI), and an open questions interview. RESULTS: Data revealed that 99.3% of refugees received some kind of support. The most frequent support (98.7%) was primary health care and the least frequent (34.7%) was support in employment and further training. The most helpful (27.5%) was primary health care, and the most detrimental (11.6%) was legal support. The most desired types of support were help in employment (31.8%) and further education/training (20.5%). The educational level of refugees affected their perceptions of support as detrimental or desired. CONCLUSIONS: There are different levels of received and desired support among host countries. There are also differences in the perception of received and desired support with regard to the refugees' educational levels