Policy and practice in an atoll territory : British rule in the Gilbert and Ellice Islands, 1892-1970.

The sixteen Gilbert and nine Ellice Islands form a chain of coral atolls and reef islands that lies between latitudes 3°30'N and 2°45'S and longitudes 172°30'E and 180° in the central Pacific Ocean. Only Butaritari, Tarawa and Abemama in the Gilberts and Nukufetau and Funafuti in the Ellice Islands offer safe lagoon anchorages for ships with a draft in excess of fifteen feet. Landing at the reef islands, for example at Nikunau and Tamana in the Gilberts or at Nanumanga and Niutao in the Ellice, can be hazardous in calm weather and is virtually impossible during westerly storms. Poor soils, composed primarily of sand and vegetal deposits, sparse and irregular rainfall, and the shallow freshwater lens associated with low coral islands (maximum altitude of about fifteen feet) all combine to place severe limitations on the range of agricultural crops that can be grown. Pandanus, breadfruit and the ubiquitous coconut are the main tree crops and a coarse taro-like plant (known as babai in the Gilberts and pulaka in the Ellice) is laboriously cultivated in pits up to eight feet in depth on all islands. A wider range of exotic crops, bananas and papaw for example,can be grown with ease in the Ellice Islands but only with difficulty on most of the Gilbert Islands. Throughout both groups, traditional systems of land tenure which have led to extensive fragmentation make effective land utilisation difficult; the problem is complicated on those atolls which consist of a string of islets spread along a reef. It is clear that, before the days of imported foodstuffs, the Gilbertese and Ellice Islanders were forced to live in a delicate balance with their environment

Campus Vol V N 2

Gillies, Jean. Cover. Picture. 0. Gould, Jim. A Christmas Carol...A Modern Tragedy . Prose. 3. MacDonald, Honnie. More Sinned Against . Prose. 4. Olwin, Lynn. Campus Calender Queens For Christmas . Poem. 7. Trimble, John. Campus Calender Queens For Christmas . Picture. 7. Bedell, Barrie and John Hodges. Shopping Guide For Christmas Prose. 15. Yearling, Joe. Sport Shorts . Prose. 16. Dresser, Bill. Tenth Anniversary . Prose. 18. Gleason, Sally. Lost Christmas . Prose. 17

Design and elaboration of a tractable tricyclic scaffold to synthesize druglike inhibitors of dipeptidyl peptidase-4 (DPP-4), antagonists of the C–C Chemokine Receptor Type 5 (CCR5), and highly potent and selective phosphoinositol-3 Kinase δ (PI3Kδ) inhibitors

A novel molecular scaffold has been synthesized, and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies, we have shown use of the tricyclic scaffold to synthesize potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs

Investigation of the deposition and emission of mercury in arctic snow during an atmospheric mercury depletion event

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94701/1/jgrd14741.pd

Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus β-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as β-arrestin recruitment. At the μ-opioid receptor (MOR), G protein–biased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in β-arrestin–mediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and β-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target

The Legacy of Leaded Gasoline in Bottom Sediment of Small Rural Reservoirs

The historical and ongoing lead (Pb) contamination caused by the 20th-century use of leaded gasoline was investigated by an analysis of bottom sediment in eight small rural reservoirs in eastern Kansas, USA. For the reservoirs that were completed before or during the period of maximum Pb emissions from vehicles (i.e., the 1940s through the early 1980s) and that had a major highway in the basin, increased Pb concentrations reflected the pattern of historical leaded gasoline use. For at least some of these reservoirs, residual Pb is still being delivered from the basins. There was no evidence of increased Pb deposition for the reservoirs completed after the period of peak Pb emissions and (or) located in relatively remote areas with little or no highway traffic. Results indicated that several factors affected the magnitude and variability of Pb concentrations in reservoir sediment including traffic volume, reservoir age, and basin size. The increased Pb concentrations at four reservoirs exceeded the U.S. Environmental Protection Agency threshold-effects level (30.2 mg kg-1) and frequently exceeded a consensus-based threshold-effects concentration (35.8 mg kg-1) for possible adverse biological effects. For two reservoirs it was estimated that it will take at least 20 to 70 yr for Pb in the newly deposited sediment to return to baseline (pre-1920s) concentrations (30 mg kg-1) following the phase out of leaded gasoline. The buried sediment with elevated Pb concentrations may pose a future environmental concern if the reservoirs are dredged, the dams are removed, or the dams fail

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response