Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Charge and current-sensitive preamplifiers for pulse shape discrimination techniques with silicon detectors

New charge and current-sensitive preamplifiers coupled to silicon detectors and devoted to studies in nuclear structure and dynamics have been developed and tested. For the first time shapes of current pulses from light charged particles and carbon ions are presented. Capabilities for pulse shape discrimination techniques are demonstrated.Comment: 14 pages, 12 figures, to be published in Nucl. Inst. Meth.

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

An Examination of Extension Professionals\u27 Demographic and Personal Characteristics Toward Fostering Diversity-Inclusive 4-H Programs

4-H youth professionals’ attitudes about the perceptions of diversity inclusion in their programs are variables that may have an influence on the number of youths that enroll in 4-H. This study examines the impact of Extension professionals’ demographic and personal characteristics on their perceptions of the benefits of diversity inclusion, perceived barriers to diversity inclusion, and proposed solutions to increase diversity inclusion in 4-H youth programs. Using a web-based questionnaire, the researchers employed a nonproportional stratified random sampling technique, and 117 Extension professionals participated. Through comparative analysis, the researcher found statistically significant differences existed in professionals’ perceptions toward the benefits of diversity inclusion, the perceived barriers toward diversity inclusion, and the proposed solutions to increase diversity inclusion in 4-H programs. Additional research should be conducted to understand better why these differences exist

Perceptions of 4-H Professionals on Proposed Solutions Towards Diversity Inclusive 4-H Youth Programs

This paper highlights findings from a web-based questionnaire used to explore and analyze [State] 4-H youth professional’s perceptions on proposed solutions to increasing diversity inclusion — particularly among youth of color and youth with disabilities — in 4-H youth programs. Descriptive statistics were used to report demographic and personal characteristics along with percentage agreements on proposed solutions. Respondents agreed that: “County 4-H youth professionals should become familiar with the youth with disabilities represented in their counties in order to promote an atmosphere of acceptance and cooperation;” “4-H youth instructional materials should reflect the diverse society that 4-H youth programs have;” and “for youth to become interested in joining 4-H, parents, 4-H youth professionals, and policymakers must develop strategies to address the different learning styles of all youth.” Finally, recommendations were identified for professionals who want to increase diversity inclusion in their respective 4-H youth programs

Assessing recent trends in high-latitude Southern Hemisphere surface climate

Understanding the causes of recent climatic trends and variability in the high-latitude Southern Hemisphere is hampered by a short instrumental record. Here, we analyse recent atmosphere, surface ocean and sea-ice observations in this region and assess their trends in the context of palaeoclimate records and climate model simulations. Over the 36-year satellite era, significant linear trends in annual mean sea-ice extent, surface temperature and sea-level pressure are superimposed on large interannual to decadal variability. Most observed trends, however, are not unusual when compared with Antarctic palaeoclimate records of the past two centuries. With the exception of the positive trend in the Southern Annular Mode, climate model simulations that include anthropogenic forcing are not compatible with the observed trends. This suggests that natural variability overwhelms the forced response in the observations, but the models may not fully represent this natural variability or may overestimate the magnitude of the forced response.Support was provided by the following organizations: N.J.A: QEII fellowship and Discovery Project awarded by the Australian Research Council (ARC DP110101161 and DP140102059); M.H.E., ARC Laureate Fellowship (FL100100214); V.M.D., Agence Nationale de la Recherche, project ANR-14-CE01-0001 (ASUMA), and logistical support to French Antarctic studies from the Institut Polaire Paul-Emile Victor (IPEV); B.S., PAGES Antarctica 2k and the ESF-PolarClimate HOLOCLIP project; H.G., the Fonds National de la Recherche Scientifique (F.R.S.-FNRS-Belgium), where he is Research Director; P.O.C., research grant ANPCyT PICT2012 2927; R.L.F., NSF grant 1341621; E.J.S., the Leverhulme Trust; S.T.G., NSF grants OCE-1234473 and PLR-1425989; D.P.S., NSF grant 1235231; NCAR is sponsored by the National Science Foundation (NSF); G.R.S., NSF grants AGS-1206120 and AGS-1407360; D.S., the French ANR CEPS project Green Greenland (ANR-10-CEPL-0008); G.J.M., UK Natural Environment Research Council (NERC) through the British Antarctic Survey research programme Polar Science for Planet Earth; A.K.M., US Department of Energy under contract DE-SC0012457; K.R.C., VUW doctoral scholarship; L.M.F., Australian Research Council (FL100100214); D.J.C., NERC grant NE/H014896/1; C.d.L., UPMC doctoral scholarship; A.J.O., EU grant FP7-PEOPLE-2012-IIF 331615; X.C., the French ANR CLIMICE (ANR-08-CEXC-012-01) and the FP7 PAST4FUTURE (243908) projects; J.A.R., Marsden grant VUW1408; I.E., NSF grant OCE-1357078; T.R.V., the Australian Government's Cooperative Research Centres programme, through the ACE CRC

The concurrent programming of saccades

Sequences of saccades have been shown to be prepared concurrently however it remains unclear exactly what aspects of those saccades are programmed in parallel. To examine this participants were asked to make one or two target-driven saccades: a reflexive saccade; a voluntary saccade; a reflexive then a voluntary saccade; or vice versa. During the first response the position of a second target was manipulated. The new location of the second saccade target was found to impact on second saccade latencies and second saccade accuracy showing that some aspects of the second saccade program are prepared in parallel with the first. However, differences were found in the specific pattern of effects for each sequence type. These differences fit well within a general framework for saccade control in which a common priority map for saccade control is computed and the influence of saccade programs on one another depends not so much on the types of saccade being produced but rather on the rate at which their programs develop

Identifying source populations for the reintroduction of the Eurasian beaver, Castor fiber L. 1758, into Britain: evidence from ancient DNA

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