In her recent book Atonement, Eleonore Stump objects to the Anselmian theory of atonement, claiming it is not consistent with God's love. I argue that her objection mischaracterizes Anselmian theories. First, Stump equivocates on the concept of forgiveness, conflating personal forgiveness with divine pardon, and second, Stump misrepresents the God of Anselm as unwilling to reconcile with sinners prior to receiving satisfaction. I suggest that Stump's real objection should be to the Anselmian view of divine justice as retributive, not to his conception of divine love. I suggest a model of an all-loving God acting as a retributive judge.

Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation.

GenomeAsia100K is a human genome project based at Nanyang Technological University in Singapore that aims to sequence one hundred thousand Asian genomes in an effort that addresses an ethnic bias towards Western populations in previous genomic research. GenomeAsia100K consists of a team of bioinformaticians, statisticians and population geneticists, and was initiated by the Nanyang Technological University in collaboration with industrial partners MedGenome (an Indian R&D company specializing in genomic data) and the California Biotech company Genentech. The GenomeAsia100K project is amongst the most ambitious precision medicine projects to date but it is not clear how the project will challenge or reshape understandings of ethnic and racial differences in Asian populations. Ian McGonigle, a scientist and cultural anthropologist, sat down with geneticist Stephan C. Schuster, the scientific chairman of GenomeAsia100K, to discuss the project and the implications of genomics for social identity in the 21st century.

Because obesity is associated with many co-morbidities, including diabetes mellitus, this study evaluated the second-meal effect of a commercial prebiotic, inulin-type fructans, and the effects of the prebiotic on faecal microbiota, metabolites and bile acids (BA). Nine overweight beagles were used in a replicated 3×3 Latin square design to test a non-prebiotic control (cellulose) against a low (equivalent to 0·5 % diet) and high dose (equivalent to 1·0 % diet) of prebiotic over 14-d treatments. All dogs were fed the same diet twice daily, with treatments provided orally via gelatin capsules before meals. On days 13 or 14 of each period, fresh faecal samples were collected, dogs were fed at 08.00 hours and then challenged with 1 g/kg body weight of maltodextrin in place of the 16.00 hours meal. Repeated blood samples were analysed for glucose and hormone concentrations to determine postprandial incremental AUC (IAUC) data. Baseline glucose, insulin and active glucagon-like peptide-1 levels were similar between all groups (P>0·10). Glucose and insulin IAUC after glucose challenge appeared lower following the high dose, but did not reach statistical relevance. Prebiotic intervention resulted in an increase in relative abundance of some Firmicutes and a decrease in the relative abundance of some Proteobacteria. Individual and total faecal SCFA were significantly increased (P<0·05) following prebiotic supplementation. Total concentration of excreted faecal BA tended to increase in dogs fed the prebiotic (P=0·06). Our results indicate that higher doses of inulin-type prebiotics may serve as modulators of gut microbiota, metabolites and BA pool in overweight dogs.

OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.

People living in poverty are particularly vulnerable to shocks, including those caused by natural disasters such as floods and droughts. This paper analyses household survey data and hydrological riverine flood and drought data for 52 countries to find out whether poor people are disproportionally exposed to floods and droughts, and how this exposure may change in a future climate. We find that poor people are often disproportionally exposed to droughts and floods, particularly in urban areas. This pattern does not change significantly under future climate scenarios, although the absolute number of people potentially exposed to floods or droughts can increase or decrease significantly, depending on the scenario and region. In particular, many countries in Africa show a disproportionally high exposure of poor people to floods and droughts. For these hotspots, implementing risk-sensitive land-use and development policies that protect poor people should be a priority.

There is a high and increasing proportion of single-parent families in Jamaica. This has raised concerns about the potential impact of single-parent families on the social, cognitive and behavioural development of children, including their sexual relationships. The aim of this study was to investigate the association between being raised in a single-parent family and age of sexual debut among young people in Jamaica. The study was cross-sectional in design, and based on a multi-stage sampling procedure. The study was conducted in July/September 2016. The study sample comprised 233 respondents (110 males and 123 females) aged from 18 to 35 years (mean 26.37 years; SD 5.46). Respondents completed a self-administered questionnaire with questions on socio-demographic characteristics, family structure, sexual debut and current sexual behaviour. Ninety-seven (41.7%) respondents grew up in single-parent families. A total of 201 (86.3%) had had sex (102 males and 99 females). Their mean age of sexual debut was 15.51 years (SD 3.41). Sixty-five (32.3%) had early sexual debut (<16 years). Respondents from single-parent families were more likely to have had early sexual debut (56.9%; n=37) compared with those from two-parent families (43.1%, n=28; p=0.004). Only 44.6% (n=29) of those who experienced early sexual debut used a condom during their first sexual encounter compared with 73% (n=100) of those who had a later sexual debut (≥16 years; p=<0.001). A single-father family structure was a significant predictor of early sexual debut (AOR 5.5; 95%CI: 1.1–25.8). The study found a significant association between single-parent family structure and age of sexual debut.

A multidecadal-scale lake-level reconstruction for Lago Wiñaymarca, the southern basin of Lake Titicaca, has been generated from diatom species abundance data. These data suggest that ~6500 cal yr BP Lago Wiñaymarca was dry, as indicated by a sediment unconformity. At ~4400 cal yr BP, the basin began to fill, as indicated by the dominance of shallow epiphytic species. It remained somewhat saline with extensive wetlands and abundant aquatic plants until ~3800 cal yr BP, when epiphytic species were replaced by planktic saline-indifferent species, suggesting a saline shallow lake. Wiñaymarca remained a relatively shallow lake that fluctuated on a multidecadal scale until ~1250 cal yr BP, when freshwater planktic species increased, suggesting a rise in lake level with a concomitant decrease in salinity. The lake became gradually fresher, dominated by deep, freshwater species from ~850 cal yr BP. By ~80 cal yr BP, saline-tolerant species were rare, and the lake was dominated by freshwater planktic diatoms, resembling the fresh and deep lake of today. These results reveal a more dynamic and chronologically specific record of lake-level fluctuations and associated ecological conditions that provide important new data for paleoclimatologists and archaeologists, to better understand human-environmental dynamics during the mid- to late Holocene.

Monitoring the glacier mass balance of summer-accumulation-type Himalayan glaciers is critical to not only assess the impact of climate change on the volume of such glaciers but also predict the downstream water availability and the global sea-level change in future. To better understand the change in meteorological parameters related to glacier mass balance and runoff in a glacierized basin and to assess the highly heterogeneous glacier responses to climate change in the Nepal Himalaya and nearby ranges, the Cryosphere Monitoring Project (CMP) carries out meteorological observations in Langtang Valley and mass-balance measurements on Yala Glacier, a debris-free glacier in the same valley. A negative annual mass balance of –0.89m w.e. and the rising equilibrium-line altitude of Yala Glacier indicate a continuation of a secular trend toward more negative mass balances. Lower temperature lapse rate during the monsoon, the effect of convective precipitation associated with mesoscale thermal circulation in the local precipitation and the occurrence of distinct diurnal cycles of temperature and precipitation at different stations in the valley are other conclusions of this comprehensive scientific study initiated by CMP which aims to yield multi-year glaciological, hydrological and meteorological observations in the glacierized Langtang River basin.

During summer 2011, seismic activity in the ablation zone of the western Greenland ice sheet (GrIS) was monitored using a network of three-component seismometers. The seismic record includes a large variety of icequakes and seismic tremors that demonstrate a clear correlation with subglacial water flow. We verified the existence of well-known shallow icequakes (related to surface crevasse formation), deep icequakes (located at 100–160 m depth) and narrow-banded short-term seismic tremors (tens of seconds in duration). In addition, we present previously unreported long-term tremors lasting several hours. Using attenuation of the measured tremor amplitude, we locate the epicentre of this long-term tremor to a large moulin within our study area. Between 3 and 11 Hz, our continuous seismic record is dominated by this ‘moulin tremor’ and shows strong correlation with the water level of the generating moulin. We argue that monitoring of icequake and glacial tremor sources bears high potential for investigating glacier hydraulics and dynamics, and is thus an ideal supplement to traditional glaciological measurements.