CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis

Objective: To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Methods: Case report with neuroimaging and pathologic data. Results: A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. Conclusions: The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity

Task force on immigration and higher education in Central Massachusetts

In August 2007, the Colleges of Worcester Consortium, Inc. created a task force to examine the issue of immigration and higher education in Central Massachusetts. It has become increasingly clear from recent demographic and economic studies and projections that the population in the northeast, and certainly in Central Massachusetts, is showing minimal growth. There is evidence that a decline in the “native-born” population is caused by significant out-migration due to a number of factors, including the high cost of living, limited career opportunities and a declining birth rate. The limited population growth that is evident is due primarily to the recent influx of immigrants to this area, with the most significant numbers in Worcester coming from Ghana, Brazil, the Dominican Republic, Kenya, El Salvador, Albania and Liberia. It is also clear that the area’s economy is becoming more knowledge-based with an increasing percentage of all new jobs requiring some form of postsecondary education. According to the 2007 Massachusetts Department of Workforce Development’s Job Vacancy Survey, 38 percent of current job vacancies in Massachusetts require an associate’s degree or higher. This represents an increase from 30 percent in 2003. Consequently, the level of education that the immigrant population attains is of vital importance to everyone—not only to immigrant students and their families but also to the economic well-being of the entire region. The Task Force was charged with researching the barriers to higher education faced by this new wave of immigrants and suggesting recommendations to address those barriers. The 36-member Task Force was made up of representatives from Consortium member institutions; federal, state and local governments; community and faithbased organizations; the Worcester Public Schools; the Massachusetts Board of Higher Education; and the Massachusetts Immigrant and Refugee Advocacy (MIRA) Coalition. Meetings were held over six months, during which the Task Force identified three main barriers faced by immigrant communities in accessing higher education, and sub-committees were created to work on each of these. Speakers were invited to present on topics of interest. Two public hearings were held, the first of which was conducted at Worcester State College in October. It attracted community representatives, as well as college and high school faculty and administrators. The second hearing, held at the downtown branch of Quinsigamond Community College (QCC) in December, was attended by immigrants (English for Speakers of Other Languages – ESOL and GED) students as well as QCC staff.Published versio

Secular trends in reported portion size of food and beverages consumed by Irish adults

The present analysis aimed to investigate the changes in the reported portion sizes (PS) of foods and beverages commonly consumed by Irish adults (18–64 years) from the North South Ireland Food Consumption Survey (NSIFCS) (1997–2001) and the National Adult Nutrition Survey (NANS) (2008–10). Food PS, which are defined as the weight of food (g) consumed per eating occasion, were calculated for comparable foods and beverages in two nationally representative cross-sectional Irish food consumption surveys and were published in NSIFCS and NANS. Repeated measure mixed model analysis compared reported food PS at the total population level as well as subdivided by sex, age, BMI and social class. A total of thirteen commonly consumed foods were examined. The analysis demonstrated that PS significantly increased for five foods (‘white sliced bread’, ‘brown/wholemeal breads’, ‘all meat, cooked’, ‘poultry, roasted’ and ‘milk’), significantly decreased for three (‘potatoes’, ‘chips/wedges’ and ‘ham, sliced’) and did not significantly change for five foods (‘processed potato products’, ‘bacon/ham’, ‘cheese’, ‘yogurt’ and ‘butter/spreads’) between the NSIFCS and the NANS. The present study demonstrates that there was considerable variation in the trends in reported food PS over this period

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

FGF4 and Retinoic Acid Direct Differentiation of hESCs into PDX1-Expressing Foregut Endoderm in a Time- and Concentration-Dependent Manner

BACKGROUND: Retinoic acid (RA) and fibroblast growth factor 4 (FGF4) signaling control endoderm patterning and pancreas induction/expansion. Based on these findings, RA and FGFs, excluding FGF4, have frequently been used in differentiation protocols to direct differentiation of hESCs into endodermal and pancreatic cell types. In vivo, these signaling pathways act in a temporal and concentration-dependent manner. However, in vitro, the underlying basis for the time of addition of growth and differentiation factors (GDFs), including RA and FGFs, as well as the concentration is lacking. Thus, in order to develop robust and reliable differentiation protocols of ESCs into mature pancreatic cell types, including insulin-producing beta cells, it will be important to mechanistically understand each specification step. This includes differentiation of mesendoderm/definitive endoderm into foregut endoderm--the origin of pancreatic endoderm. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide data on the individual and combinatorial role of RA and FGF4 in directing differentiation of ActivinA (AA)-induced hESCs into PDX1-expressing cells. FGF4's ability to affect endoderm patterning and specification in vitro has so far not been tested. By testing out the optimal concentration and timing of addition of FGF4 and RA, we present a robust differentiation protocol that on average generates 32% PDX1(+) cells. Furthermore, we show that RA is required for converting AA-induced hESCs into PDX1(+) cells, and that part of the underlying mechanism involves FGF receptor signaling. Finally, further characterization of the PDX1(+) cells suggests that they represent foregut endoderm not yet committed to pancreatic, posterior stomach, or duodenal endoderm. CONCLUSION/SIGNIFICANCE: In conclusion, we show that RA and FGF4 jointly direct differentiation of PDX1(+) foregut endoderm in a robust and efficient manner. RA signaling mediated by the early induction of RARbeta through AA/Wnt3a is required for PDX1 expression. Part of RA's activity is mediated by FGF signaling

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)