Benchmark Calculations for Perchlorate from Three Human Cohorts

The presence of low concentrations of perchlorate in some drinking water sources has led to concern regarding potential effects on the thyroid. In a recently published report, the National Academy of Sciences indicated that the perchlorate dose required to cause hypothyroidism in adults would probably be > 0.40 mg/kg-day for months or longer. In this study, we calculated benchmark doses for perchlorate from thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) serum indicators from two occupational cohorts with long-term exposure to perchlorate, and from a clinical study of volunteers exposed to perchlorate for 2 weeks. The benchmark dose for a particular serum indicator was defined as the dose predicted to cause an additional 5 or 10% of persons to have a serum measurement outside of the normal range. Using the data from the clinical study, we estimated the half-life of perchlorate in serum at 7.5 hr and the volume of distribution at 0.34 L/kg. Using these estimates and measurements of perchlorate in serum or urine, doses in the occupational cohorts were estimated and used in benchmark calculations. Because none of the three studies found a significant effect of perchlorate on TSH or free T(4), all of the benchmark dose estimates were indistinguishable from infinity. The lower 95% statistical confidence limits on benchmark doses estimated from a combined analysis of the two occupational studies ranged from 0.21 to 0.56 mg/kg-day for free T(4) index and from 0.36 to 0.92 mg/kg-day for TSH. Corresponding estimates from the short-term clinical study were within these ranges

Redetermination of para-aminopyridine (fampridine, EL-970) at 150 K

The structure of fampridine (EL-970) or 4-aminopyridine, C₅H₆N₂, has been redetermined at 150 K. The room-temperature structure has been reported previously [Chao & Schempp (1977). Acta Cryst. B33, 1557-1564]. Pyramidalization at the amine N atom occurs in fampridine, with the N atom 0.133 (11) Å from the plane of the three C/H/H atoms to which it is bonded; the interplanar angle between the pyridyl ring and NH2 group is 21 (2)°. Aggregation in the solid state occurs by N-H...N and N-H...[pi](pyridine) interactions with N...N and N...[pi](centroid) distances of 2.9829 (18) and 3.3954 (15) Å, respectively; a C-H...[pi](pyridine) contact completes the intermolecular interactions [C...[pi](centroid) = 3.6360 (16) Å]

Ethyl and isopropyl 4-ferrocenylbenzoate.

The title compounds, [Fe(C5H5)(C14H13O2)] and [Fe(C5H5)- (C15H15O2)], respectively, contain the ferrocenyl 5(C5H4) and phenylene ±C6H4± rings in a nearly coplanar arrangement, with interplanar angles of 6.88 (12) and 10.5 (2), respectively. Molecules of the ethyl ester form dimers through 5(C5H5)CÐ H O C hydrogen bonds, with graph set R22 (20), and, together with Csp3ÐH (C5H5) interactions, generate a one-dimensional column (irregular ladder). Molecules of the isopropyl ester aggregate through 5(C5H5)CÐH (C6H4) interactions

Providing Diverse Trainees an Early and Transparent Introduction to Academic Appointment and Promotion Processes.

IntroductionThe growth in number of medical schools and increased numbers of faculty tracks have combined with evolving criteria for promotion to trigger a call for greater transparency of academic appointment and promotion processes. Most vulnerable to confusion about these changes are first-generation and diverse medical students and residents, the upstream pipeline of the academic medicine workforce. Diverse medical students have expressed diminished interest in academia because of perceived obstacles in appointment and promotion processes.MethodsThis workshop was designed to utilize didactics and career reflection exercises to help trainees learn: (1) how to define core terms related to academic appointment and promotion processes, (2) how to compare data elements for different CVs and portfolios, (3) common steps in submitting a promotion package, and (4) that they can immediately begin to document content for academic CVs, portfolios, and promotion packages.ResultsOne hundred forty-five diverse participants completed an evaluation at eight conferences across the U.S. More than 90% strongly agreed or agreed that the aforementioned objectives were met. Participants commented that the workshop was "illuminating," was "very informative," and "provided an inside look of how faculty are evaluated." Results showed an immediate impact on participants' self-reported confidence to negotiate appointment and promotion processes.DiscussionIncreases in self-rated confidence to negotiate appointment and promotion processes may help sustain trainees' interest in becoming future faculty. Further monitoring will be needed to determine if early exposure to these concepts improves probability of seeking, obtaining, and maintaining appointments

Intramolecular N-H...O, intermolecular O-H...O, C-H...O and Csp³-H...πarene interactions in (2S)-2-{[(2R)-2-hydroxy-2-phenylethanoyl]amino}-4-methylpentanoic acid

The title compound, C₁₄H₁₉NO₄, forms a hydrogenbonded network in the solid state, consisting of one intramolecular N--H...O [N...O 2.569 (3)Å] and two intermolecular O--H...0=C [O...O 2.704(2) and 2.801 (2)Å] hydrogen bonds, with weaker C--H...O [C...O 3.344(3)Å] and Csp³--H...πarene [shortest C...C 3.873 (4)Å] interactions completing the three-dimensional network

Langley's CSI evolutionary model: Phase O

A testbed for the development of Controls Structures Interaction (CSI) technology to improve space science platform pointing is described. The evolutionary nature of the testbed will permit the study of global line-of-sight pointing in phases 0 and 1, whereas, multipayload pointing systems will be studied beginning with phase 2. The design, capabilities, and typical dynamic behavior of the phase 0 version of the CSI evolutionary model (CEM) is documented for investigator both internal and external to NASA. The model description includes line-of-sight pointing measurement, testbed structure, actuators, sensors, and real time computers, as well as finite element and state space models of major components

Effect of supplementation with n-3 polyunsaturated fatty acids and/or β-glucans on performance, feeding behaviour and immune status of Holstein Friesian bull calves during the pre- and post-weaning periods

peer-reviewedBackground Previous research in both calves and other species has suggested n-3 polyunsaturated fatty acids (PUFA) and β-glucans may have positive effects on immune function. This experiment measured performance, behaviour, metabolite and immunological responses to pre-weaning supplementation of dairy bull calves with n-3 PUFA in the form of fish oil and β-glucans derived from seaweed extract. 44 Holstein Friesian bull calves, aged 13.7 ± 2.5 d and weighing 48.0 ± 5.8 kg were artificially reared using an electronic feeding system. Each calf was offered 5 L (120 g/L) per day of milk replacer (MR) and assigned to one of four treatments included in the MR, (1) Control (CON); (2) 40 g n-3 PUFA per day (FO); (3) 1 g β-glucans per day (GL) and (4) 40 g n-3 PUFA per day & 1 g/d β-glucans (FOGL) in a 2 × 2 factorial design. Milk replacer and concentrate was offered from d 0–62 (pre-weaning), while concentrate provision continued for a further 31 d post-weaning period. Individual daily feed intake and feeding behaviour was recorded throughout, while bodyweight and blood analyte data were collected at regular intervals. Results Overall mean concentrate DMI from d 0–93 was 1.39, 1.27, 1.00 and 0.72 kg/d for CON, FO, GL and FOGL calves, respectively (SEM = 0.037; P < 0.0001). Calves supplemented with GL were significantly lighter (P < 0.0001) at both weaning (d 62) and turnout to pasture (d 93) than un-supplemented calves, with a similar effect (P < 0.0001) evident for calves receiving FO compared to un-supplemented contemporaries. Supplementation with GL reduced the number of unrewarded visits where milk was not consumed (P < 0.0001) while supplementation with FO increased mean drinking speed (P < 0.0001). Supplementation with GL resulted in greater concentrations of haptoglobin (P = 0.034), greater serum osmolality (P = 0.021) and lower lymphocyte levels (P = 0.027). In addition, cells from GL supplemented calves exhibited a lower response than un-supplemented contemporaries to both Phytohaemagglutinin A stimulated IFN-γ (P = 0.019) and Concanavalin A stimulated IFN-γ (P = 0.012) following in vitro challenges. Conclusions Pre-weaning supplementation of bull calves with either n-3 PUFA or β-glucan resulted in reduced voluntary feed intake of concentrate and consequently poorer pre-weaning calf performance. There was no evidence for any beneficial effect of either supplementation strategy on calves’ immune responses