Adapting the International System of Units to the twenty-first century

We review the proposal of the International Committee for Weights and Measures (Comité International des Poids et Mesures, CIPM), currently being considered by the General Conference on Weights and Measures (Conférences Générales des Poids et Mesures, CGPM), to revise the International System of Units (Le Système International d’Unitès, SI). The proposal includes new definitions for four of the seven base units of the SI, and a new form of words to present the definitions of all the units. The objective of the proposed changes is to adopt definitions referenced to constants of nature, taken in the widest sense, so that the definitions may be based on what are believed to be true invariants. In particular, whereas in the current SI the kilogram, ampere, kelvin and mole are linked to exact numerical values of the mass of the international prototype of the kilogram, the magnetic constant (permeability of vacuum), the triple-point temperature of water and the molar mass of carbon-12, respectively, in the new SI these units are linked to exact numerical values of the Planck constant, the elementary charge, the Boltzmann constant and the Avogadro constant, respectively. The new wording used expresses the definitions in a simple and unambiguous manner without the need for the distinction between base and derived units. The importance of relations among the fundamental constants to the definitions, and the importance of establishing a mise en pratique for the realization of each definition, are also discussed

Depressive symptoms in asymptomatic stage B heart failure with Type II diabetic mellitus.

BackgroundThe presence of concomitant Type II diabetic mellitus (T2DM) and depressive symptoms adversely affects individuals with symptomatic heart failure (HF).HypothesisIn presymptomatic stage B HF, this study hypothesized the presence of greater inflammation and depressive symptoms in T2DM as compared to non-T2DM Stage B patients.MethodsThis cross-sectional study examined clinical parameters, inflammatory biomarkers, and depressive symptoms in 349 T2DM and non-T2DM men with asymptomatic stage B HF (mean age 66.4 years ±10.1; range 30-91).ResultsFewer diabetic HF patients had left ventricular (LV) systolic dysfunction (P < .05) although more had LV diastolic dysfunction (P < .001). A higher percentage of T2DM HF patients were taking ACE-inhibitors, beta-blockers, calcium channel blockers, statins, and diuretics (P values < .05). T2DM HF patients had higher circulating levels of interleukin-6 (IL-6) (P < .01), tumor necrosis factor-alpha (P < .01), and soluble ST2 (sST2) (P < .01) and reported more somatic/affective depressive symptoms (Beck Depression Inventory II) (P < .05) but not cognitive/affective depressive symptoms (P = .20). Among all patients, in a multiple regression analysis predicting presence of somatic/affective depressive symptoms, sST2 (P = .026), IL-6 (P = .010), B-type natriuretic peptide (P = .016), and sleep (Pittsburgh Sleep Quality Index [P < .001]) were significant predictors (overall model F = 15.39, P < .001, adjusted R2 = .207).ConclusionsSomatic/affective but not cognitive/affective depressive symptoms are elevated in asymptomatic HF patients with T2DM patients. Linkages with elevated inflammatory and cardiac relevant biomarkers suggest shared pathophysiological mechanisms among T2DM HF patients with somatic depression, and these conditions are responsive to routine interventions, including behavioral. Copyright © 2019 John Wiley & Sons, Ltd

Crystal structures of type-II inositol polyphosphate 5-phosphatase INPP5B with synthetic inositol polyphosphate surrogates reveal new mechanistic insights for the inositol 5-phosphatase family

The inositol polyphosphate 5-phosphatase INPP5B hydrolyzes the 5-phosphate group from water- and lipid-soluble signaling messengers. Two synthetic benzene and biphenyl polyphosphates (BzP/BiPhPs), simplified surrogates of inositol phosphates and phospholipid headgroups, were identified by thermodynamic studies as potent INPP5B ligands. The X-ray structure of the complex between INPP5B and biphenyl 3,3,4,4,5,5-hexakisphosphate [BiPh(3,3,4,4,5,5)P6, IC50 5.5 μM] was determined at 2.89Å resolution. One inhibitor pole locates in the phospholipid headgroup binding site and the second solvent-exposed ring binds to the His-Tag of another INPP5B molecule, while a molecule of inorganic phosphate is also present in the active site. Benzene 1,2,3-trisphosphate [Bz(1,2,3)P3] [one ring of BiPh(3,3,4,4,5,5)P6] inhibits INPP5B ca 6-fold less potently. Co-crystallization with benzene 1,2,4,5-tetrakisphosphate [Bz(1,2,4,5)P4, IC50 = 6.3 μM] yielded a structure refined at 2.9Å resolution. Conserved residues among the 5-phosphatase family mediate similar interactions with Bz(1,2,4,5)P4 and BiPh(3,3',4,4',5,5')P6 to those with the polar groups present in positions 1,4,5 and 6 on the inositol ring of the substrate. 5-Phosphatase specificity most likely resides in the variable zone located close to the 2- and 3-positions of the inositol ring. We propose that the inorganic phosphate present in the INPP5BBiPh(3,3,4,4,5,5)P6 complex mimics the post-cleavage substrate 5-phosphate released by INPP5B in the catalytic site, allowing elucidation of two new key features in the catalytic mechanism proposed for the family of phosphoinositide 5-phosphatases: first, the involvement of the conserved Arg-451 in the interaction with the 5-phosphate and secondly, identification of the water molecule that initiates 5-phosphate hydrolysis. Our model also has implications for the proposed moving metal mechanism

Development and Delivery of a Quality Improvement Program to Reduce Antipsychotic Polytherapy

BACKGROUND: Although antipsychotic polytherapy is considered appropriate in limited circumstances (e.g., during a brief “cross-titration” period when switching medications), its increasing prevalence indicates use beyond this limited scope. Despite absence of support in the medical literature and higher costs, antipsychotic polytherapy is common in the treatment of schizophrenia and related disorders. The highest utilization of antipsychotic polytherapy occurs on psychiatric inpatient units, and in 2008, the Joint Commission released the first set of 7 hospital-based inpatient psychiatric services (HBIPS) core measures, 2 of which assess antipsychotic polytherapy at time of discharge. OBJECTIVE: To describe the effect on antipsychotic polytherapy at time of discharge of a 2-part quality improvement program composed of educational seminars and prescriber-specific feedback provided to 11 psychiatrists in 4 acute inpatient psychiatric units in 2 hospitals. METHODS: In a regional academic health care system, we determined the prevalence of antipsychotic monotherapy and polytherapy at time of discharge for all patients discharged on standing antipsychotic medications during 3 periods: (a) a 3-month baseline period (August 2006 through October 2006); (b) in July 2007, after delivery of 4 educational luncheon seminars to 11 psychiatrists from November 2006 through June 2007; and (c) in June 2008, following the provision of monthly prescriber-specific audit feedback from August 2007 through June 2008. To prepare nurses for the change and address possible safety concerns, an educational module was delivered to the psychiatric nursing staff at “best practice” day lectures held in the first quarter of 2007. General themes in the educational presentations included literature-based reviews of (a) safety and efficacy of antipsychotic polytherapy, (b) medical risks of antipsychotic medications, (c) specific versus nonspecific effects of these medications, and (d) effectiveness of first- versus second-generation antipsychotic medications. The prescriber-specific audit feedback was provided in paper form and masked the identity of the other prescribers. The chief of service reviewed audit feedback individually with each psychiatrist on a quarterly basis. The primary outcome measure was the percentage of patients prescribed 2 or more antipsychotics at discharge. A secondary outcome measure was the percentage of patients prescribed 3 or more antipsychotics at discharge. Differences in the primary outcome measure, comparing (a) July 2007 with the baseline period and (b) June 2008 with July 2007, were analyzed using Fisher’s Exact tests. The Cochran-Armitage test for trend was used to assess the relationship between the primary outcome measure and the extent of the intervention, measured as the 3 time periods. For the secondary outcome measure, the Goodman-Kruskal gamma test for ordered categorical data was calculated to examine the association between the proportion of patients receiving 1, 2, or 3 or more antipsychotics at discharge and the 3 time periods. RESULTS: The percentage of patients prescribed 2 or more antipsychotics at discharge declined from 33.9% at baseline (132 of 389 patients), to 21.8% after delivery of the educational modules (44 of 202 patients, P = 0.002), and to 12.2% after audit feedback (18 of 147 patients, P = 0.023; Cochran-Armitage test for trend P \u3c 0.001). When antipsychotic use was classified as 1, 2, or 3 or more antipsychotic medications, more extensive intervention was associated with decreased combination use (Goodman-Kruskal gamma = 0.39, P \u3c 0.001). In the baseline period, 5.9% of patients were prescribed 3 or more antipsychotics at discharge. Following completion of the educational and audit components, respectively, the proportion of patients prescribed 3 or more antipsychotics declined to 2.5% and then to 0.0%. CONCLUSION: Educational modules presented to psychiatrists and nurses in group settings were associated with a decrease in the rate of prescribing 2 or more antipsychotics at discharge from acute psychiatric inpatient units. Addition of monthly audit feedback provided to psychiatrists was associated with further decreases

Natural history of Sin Nombre virus in western Colorado.

A mark-recapture longitudinal study of immunoglobulin G (IgG) antibody to Sin Nombre virus (SNV) in rodent populations in western Colorado (1994-results summarized to October 1997) indicates the presence of SNV or a closely related hantavirus at two sites. Most rodents (principally deer mice, Peromyscus maniculatus, and pinyon mice, P. truei) did not persist on the trapping webs much beyond 1 month after first capture. Some persisted more than 1 year, which suggests that even a few infected deer mice could serve as transseasonal reservoirs and mechanisms for over-winter virus maintenance. A positive association between wounds and SNV antibody in adult animals at both sites suggests that when infected rodents in certain populations fight with uninfected rodents, virus amplification occurs. At both sites, male rodents comprised a larger percentage of seropositive mice than recaptured mice, which suggests that male mice contribute more to the SNV epizootic cycle than female mice. In deer mice, IgG antibody prevalence fluctuations were positively associated with population fluctuations. The rates of seroconversion, which in deer mice at both sites occurred mostly during late summer and midwinter, were higher than the seroprevalence, which suggests that the longer deer mice live, the greater the probability they will become infected with SNV

Brief report: Characteristics of antidepressant use in patients with heart failure

Paul J Mills1, Joel E Dimsdale1, Suzi Hong1, Geoffrey Van Den Brande2, Laura Redwine2, Barry H Greenberg2, Thomas Rutledge11Department of Psychiatry; 2Department of Medicine, University of California San Diego, La Jolla, CA, USABackground: Depression is common in heart failure (HF), but there is little data on the characteristics of antidepressant use in patients with HF.Objective: To survey basic information on antidepressant prescription characteristics, use, effectiveness, and follow-up.Methods: Observational study in two outpatient cardiology clinics of 37 NYHA class I–IV HF patients taking antidepressant medication.Results: Thirty-one percent of prescriptions for antidepressants were obtained from psychiatrists, 58% from primary care physicians, and 8% from cardiologists. The majority of patients (87%) reported regularly taking their antidepressant medication as prescribed, however 48% reported never having had the dosage of their antidepressant medication adjusted. Only 53% of the patients reported that the medication had helped their mood “almost entirely” or “mostly” back to normal since starting their antidepressants, while the remaining patients reported that their mood was only “halfway” or “somewhat” back to normal or that the medication had not helped their depression at all. Among a subset of 10 patients who completed the Beck Depression (BDI) inventory, 6 still had depressed mood (BDI ≥ 10).Conclusion: The findings from this survey study provide insight into the characteristics of antidepressant use in patients with HF and argue for better follow up of HF patients who are prescribed antidepressants.Keywords: heart failure, antidepressant medication, adherence, effectivenes

PUBLIC HEALTH Assessment of Ecologic and Biologic Factors Leading to Hantavirus Pulmonary Syndrome, Colorado, U.S.A

Aim. To understand the ecologic parameters of Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) infections in the deer mouse (Peromyscus maniculatus), environmental variables impacting the rodent populations, and the conditions under which SNV is amplified. This may help us understand the antecedents of human risk for developing hantavirus pulmonary syndrome (HPS) as a consequence of SNV infection. Method. Each 6 weeks, we trapped, measured, tagged, bled, and released rodents at three widely spaced sites in Colorado, USA: Fort Lewis (1994Lewis ( -2001, Molina (1994Molina ( -2001, and Pinyon Canyon Maneuver Site (1995)(1996)(1997)(1998)(1999)(2000)(2001). The ELISA method was used to test rodent blood samples for IgG antibody to SNV antigen. Results. Where rodent species richness was high, the prevalence of infection of deer mice (as determined by the presence of antibody) with SNV was low, and vice versa. There was a higher prevalence of antibody to SNV in male than in female rodents, and seasonal differences were observed in acquisition of SNV between male and female deer mice. Long-lived infected deer mice served as transseasonal, over-winter reservoirs for the virus, providing the mechanism for its survival. Conclusion. Prevalence of rodent infection appears to be associated with fluctuations in deer mouse populations and, indirectly, with timing and amount of precipitation and the resulting biologic events (a "trophic cascade"). Together with information regarding transseasonal maintenance of SNV, seasonal differences in acquisition of SNV between sexes, group foraging, and various other factors may expand our understanding of the risk factors for acquiring HPS. Taken together and applied, we anticipate developing methods for preventing this disease as well as diseases caused by other rodent-borne viruses

Population Dynamics Of A Diverse Rodent Assemblage In Mixed Grass-Shrub Habitat, Southeastern Colorado, 1995–2000

We followed seasonal and year-to-year population dynamics for a diverse rodent assemblage in a short-grass prairie ecosystem in southeastern Colorado (USA) for 6 yr. We captured 2,798 individual rodents (range, one to 812 individuals per species) belonging to 19 species. The two most common species, deer mice (Peromyscus maniculatus) and western harvest mice (Reithrodontomys megalotis), generally had population peaks in winter and nadirs in summer; several other murid species demonstrated autumn peaks and spring nadirs; heteromyids were infrequently captured in winter, and populations generally peaked in summer or autumn. Interannual trends indicated an interactive effect between temperature and precipitation. Conditions associated with low rodent populations or population declines were high precipitation during cold periods (autumn and winter) and low precipitation during warm periods (spring and summer). Severity of adverse effects varied by species. Heteromyids, for example, were apparently not negatively affected by the hot, dry spring and summer of 2000. Cross-correlations for the temporal series of relative population abundances between species pairs (which are affected by both seasonal and interannual population dynamics) revealed positive associations among most murids and among most heteromyids, but there were negative associations between murids and heteromyids. These results have important implications for those attempting to model population dynamics of rodent populations for purposes of predicting disease risk

Demographic Factors Associated With Prevalence Of Antibody To Sin Nombre Virus In Deer Mice In The Western United States

We used long-term data collected for up to 10 yr (1994–2004) at 23 trapping arrays (i.e., webs and grids) in Arizona, Colorado, Montana, and New Mexico to examine demographic factors known or suspected to be associated with risk of infection with Sin Nombre virus (SNV) in its natural host, the deer mouse (Peromyscus maniculatus). Gender, age (mass), wounds or scars, season, and local relative population densities were statistically associated with the period prevalence of antibody (used as a marker of infection) to SNV in host populations. Nevertheless, antibody prevalence and some of the risk factors associated with antibody prevalence, such as relative population density, gender bias, and prevalence of wounding, varied significantly among sites and even between nearby trapping arrays at a single site. This suggests that local micrositespecific differences play an important role in determining relative risk of infection by SNV in rodents and, consequently, in humans. Deer mouse relative population density varied among sites and was positively and statistically associated with infection prevalence, an association that researchers conducting shorter-term studies failed to demonstrate. Both wounding and antibody prevalence increased with mass class in both males and females; this increase was much more pronounced in males than in females and wounding was more frequent in adult males than in adult females. Prevalence of wounding was greatest among seropositive deer mice, regardless of mass class, but many deer mice without detectable wounds or scars eventually became infected. Many of these patterns, which will be useful in the development of predictive models of disease risk to humans, were only detected through the application of data collected over a long (10-yr) period and with abundant replication