The influence of ship motion of manual control skills

The effects of ship motion on a range of typical manual control skills were examined on the Warren Spring ship motion simulator driven in heave, pitch, and roll by signals taken from the frigate HMS Avenger at 13 m/s (25 knots) into a force 4 wind. The motion produced a vertical r.m.s. acceleration of 0.024g, mostly between 0.1 and 0.3 Hz, with comparatively little pitch or roll. A task involving unsupported arm movements was seriously affected by the motion; a pursuit tracking task showed a reliable decrement although it was still performed reasonably well (pressure and free moving tracking controls were affected equally by the motion); a digit keying task requiring ballistic hand movements was unaffected. There was no evidence that these effects were caused by sea sickness. The differing response to motion of the different tasks, from virtual destruction to no effect, suggests that a major benefit could come from an attempt to design the man/control interface onboard ship around motion resistant tasks

The Comorbidity and Temporal Relationship Between Anxiety Disorders, Eating Disorders, and Personality Disorders

Background - Population-level data on the prevalence of comorbidity between anxiety-, eating-, and personality disorders remain relatively unexplored. Additionally, the potential existence of a temporal relationship among these three classes of mental disorder is also of interest. Methods - Lifetime prevalence of, and temporal relationships among, anxiety-, eating-, and personality disorders were assessed using Part II WHO Composite International Diagnostic Interview data from the National Comorbidity Survey- Replication, a nationally representative household survey (n=5692). Results - Lifetime prevalence estimates for any anxiety-, eating-, and personality disorder were 59.8%, 2.8%, and 13.5%, respectively, among those diagnosed with at least one core (Axis I of DSM-IV) disorder. Of respondents diagnosed with any eating disorder, 31.1% also met criteria for at least one personality disorder during their lifetime (OR=3.01, CI=2.13–4.23). Forty-nine respondents met criteria for all three types of mental disorders (OR=3.73, CI=2.61–5.33). Mean age of onset for any anxiety- or eating disorder was significantly younger in respondents who were diagnosed with lifetime comorbidity (M=11.8 and 18.7, respectively) than respondents with no comorbidity during their life (M=15.1 and 23.3), ps\u3c0.01. Of respondents who met diagnostic criteria for at least one anxiety- and eating disorder, 82.6% experienced anxiety symptoms prior to their symptoms of any eating disorder. The average difference in age of onset between anxiety and eating disorders between those with and without personality disorders was not found to be statistically significant. Conclusions - Earlier development of key mental health disorders may signify those at greater risk for comorbidity during their lifetime, making earlier detection and interventions critical

Increasing the Labor-Related Costs of Business Transfers and Acquisitions—The Spectre of Per Se Liability for New Owners

This survey begins in Part II with an examination of the 1973 Supreme Court decision in Golden State Bottling Co. v. NLRB,. That decision has served as the touchstone for the rapid expansion of successor liability from the National Labor Relations Act (NLRA) to other federal labor statutes and state law. Part III marks the evolution of successor liability under the NLRA. Part IV chronicles the transfer of liabilities to other federal statutes and state laws, and Part V forecasts liabilities likely to be imposed under other statutes. Part VI describes the evolution of the successorship doctrine into an anticompetitive restraint on business transferability which replaces consideration of managerial prerogative with nearly per se liability. Finally, the last section offers new owners some practical options for avoiding or indemnifying these liabilities, but reluctantly concludes that in most transfers the new owner is now the de jure surety for any of the predecessor\u27s labor-related obligations

Low dose novel PARP-PI3K inhibition via nanoformulation improves colorectal cancer immunoradiotherapy

Multimodal therapy is often used in oncology to overcome dosing limitations and chemoresistance. Recently, combination immunoradiotherapy has shown great promise in a select subset of patients with colorectal cancer (CRC). Furthermore, molecularly targeted agents delivered in tandem with immunotherapy regimens have been suggested to improve treatment outcomes and expand the population of responding patients. In this study, radiation-sensitizing small molecules niraparib (PARP inhibitor) and HS-173 (PI3K inhibitor) are identified as a novel combination that synergistically enhance toxicity and induce immunogenic cell death both in vitro and in vivo in a CRC model. These inhibitors were co-encapsulated in a polymer micelle to overcome solubility limitations while minimizing off-target toxicity. Mice bearing syngeneic colorectal tumors (CT26) were administered these therapeutic micelles in combination with X-ray irradiation and anti-CTLA-4 immunotherapy. This combination led to enhanced efficacy demonstrated by improved tumor control and increased tumor infiltrating lymphocytes. This report represents the first investigation of DNA damage repair inhibition combined with radiation to potentiate anti-CTLA-4 immunotherapy in a CRC model.Peer reviewe

Effect of Intragastric pH on the Absorption of Oral Zinc Acetate and Zinc Oxide in Young Healthy Volunteers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142255/1/jpen0393.pd

A maximum rupture model for the central and southern Cascadia subduction zone—reassessing ages for coastal evidence of megathrust earthquakes and tsunamis

A new history of great earthquakes (and their tsunamis) for the central and southern Cascadia subduction zone shows more frequent (17 in the past 6700 yr) megathrust ruptures than previous coastal chronologies. The history is based on along-strike correlations of Bayesian age models derived from evaluation of 554 radiocarbon ages that date earthquake evidence at 14 coastal sites. We reconstruct a history that accounts for all dated stratigraphic evidence with the fewest possible ruptures by evaluating the sequence of age models for earthquake or tsunami contacts at each site, comparing the degree of temporal overlap of correlated site age models, considering evidence for closely spaced earthquakes at four sites, and hypothesizing only maximum-length megathrust ruptures. For the past 6700 yr, recurrence for all earthquakes is 370–420 yr. But correlations suggest that ruptures at ∼1.5 ka and ∼1.1 ka were of limited extent (<400 km). If so, post-3-ka recurrence for ruptures extending throughout central and southern Cascadia is 510–540 yr. But the range in the times between earthquakes is large: two instances may be ∼50 yr, whereas the longest are ∼550 and ∼850 yr. The closely spaced ruptures about 1.6 ka may illustrate a pattern common at subduction zones of a long gap ending with a great earthquake rupturing much of the subduction zone, shortly followed by a rupture of more limited extent. The ruptures of limited extent support the continued inclusion of magnitude-8 earthquakes, with longer ruptures near magnitude 9, in assessments of seismic hazard in the region

Seismic Reflection Imaging of the Low-Angle Panamint Normal Fault System, Eastern California

Shallowly dipping (<30°) low-angle normal faults (LANFs) have been documented globally; however, examples of active LANFs in continental settings are limited. The western margin of the Panamint Range in eastern California is defined by a LANF that dips west beneath Panamint Valley and has evidence of Quaternary motion. In addition, high-angle dextral-oblique normal faults displace middle to late Quaternary alluvial fans near the range front. To image shallow (<1 km depth), crosscutting relationships between the low- and high-angle faults along the range front, we acquired two high-resolution P wave seismic reflection profiles. The northern, 4.6-km-long profile crosses the 2-km-wide Wildrose graben and the southern, 0.8-km-long profile extends onto the Panamint Valley playa, ~7.5 km S of Ballarat, CA. The profile across the Wildrose graben reveals a robust, low-angle reflector interpreted to represent the LANF separating Plio-Pleistocene alluvial fanglomerate and Proterozoic metasedimentary deposits. High-angle faults interpreted in the seismic profile correspond to fault scarps on Quaternary alluvial fan surfaces. Interpretation of the reflection data suggests that the high-angle faults vertically displace the LANF up to 80 m within the Wildrose graben. Similarly, the profile south of Ballarat reveals a low-angle reflector, which appears both rotated and displaced up to 260 m by high-angle faults. These results suggest that near the Panamint range front, the high-angle faults are the dominant active structures. We conclude that at least at shallow (<1 km) depths, the LANF we imaged is not active today

High viscosity hydroxypropylmethylcellulose reduces postprandial blood glucose concentrations in NIDDM patients

The ability of high viscosity hydroxypropylmethylcellulose (HPMC) to reduce postprandial glucose concentrations was assessed in patients with non-insulin-dependent diabetes (NIDDM) and healthy volunteers. The study design consisted of a two-way crossover, single-dose administration of 10 g prehydrated high viscosity HPMC, or placebo, with a standard carbohydrate-rich meal. In patients with NIDDM, HPMC reduced blood glucose concentrations at the 60-, 75-, 90-, 120- and 150-min sampling intervals, with an average reduction in the maximum postprandial blood glucose concentration, Cmax, of 24% (P Tmax, remained unchanged. The area under the blood concentration versus time plot, AUC0-6h, was reduced by an average of 15% (P Cmax, Tmax and AUC0-6h) were unchanged. These results suggest that alterations in the blood glucose profile are mediated by luminal events rather than by changes in hormonal response. In contrast to the NIDDM patients, neither the pharmacokinetic parameters nor the blood glucose concentrations at specific sampling times were significantly affected by the coadministration of HPMC in healthy volunteers. Overall, the results of this study suggest that HPMC may be a useful adjunct in the management of NIDDM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30526/1/0000158.pd

The Scientific Foundation for Personal Genomics: Recommendations from a National Institutes of Health–Centers for Disease Control and Prevention Multidisciplinary Workshop

The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed