Barriers to Influenza Immunization: The Role of Physician Training on Influenza Vaccine Utilization in Six to Twenty-Three Month Old Infants

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Sequence Requirements for the Nuclear Localization of the Murine Cytomegalovirus M44 Gene Product pp50

AbstractThe murine cytomegalovirus (MCMV) M44 gene product pp50 is normally present in the nuclei of virus-infected cells. During transient expression of pp50 in COS-1 cells, the phosphoprotein was readily detectable in the nuclei, indicating that it possesses a nuclear localization signal (NLS). Studies on the subcellular locations of N- and C-terminal deletion mutants of pp50 suggested that alterations in both the C terminus and the highly conserved N-terminal domains of pp50 affect nuclear localization. In particular, the C-terminal 11 amino acids of pp50, which includes a “KKQK” motif, were able to mediate the import of a β-galactosidase fusion protein into the nucleus. The pair of lysine residues in this motif constitutes an essential element of the C-terminal NLS as mutation of this motif to AAQK directly affected the nuclear localization of either pp50 or β-galactosidase fusion proteins containing the C-terminal portion of pp50. Furthermore our results indicated that the functionality of the C-terminal NLS is dependent on the structural integrity of the highly conserved N-terminal portion of the molecule, as deletion of amino acids 157–201 alone adversely affected nuclear localization. In the absence of a functional C-terminal NLS, the subcellular localization of pp50 is sensitive to potential conformational changes induced by mutations within the N-terminal half of the molecule. Under those circumstances, mutation of the YK residues at position 22–23 or deletion of amino acids 267–283 was sufficient to produce a protein that was impaired in nuclear import or retention

Measuring soil frost depth in forest ecosystems with ground penetrating radar

Soil frost depth in forest ecosystems can be variable and depends largely on early winter air temperaturesand the amount and timing of snowfall. A thorough evaluation of ecological responses to seasonallyfrozen ground is hampered by our inability to adequately characterize the frequency, depth, durationand intensity of soil frost events. We evaluated the use of ground penetrating radar to nondestructivelydelineate soil frost under field conditions in three forest ecosystems. Soil frost depth was monitoredperiodically using a 900 MHz antenna in South Burlington, Vermont (SB), Sleepers River Watershed,North Danville, Vermont (SR) and Hubbard Brook Experimental Forest, New Hampshire (HBEF) duringwinter 2011–2012 on plots with snow and cleared of snow. GPR-based estimates were compared to datafrom thermistors and frost tubes, which estimate soil frost depth with a color indicating solution. In theabsence of snow, frost was initially detected at a depth of 8–10 cm. Dry snow up to 35 cm deep, enhancednear-surface frost detection, raising the minimum frost detection depth to 4–5 cm. The most favorablesurface conditions for GPR detection were bare soil or shallow dry snow where frost had penetrated to theminimum detectable depth. Unfavorable conditions included: standing water on frozen soil, wet snow,thawed surface soils and deep snow pack. Both SB and SR were suitable for frost detection most of thewinter, while HBEF was not. Tree roots were detected as point reflections and were readily discriminatedfrom continuous frost reflections. The bias of GPR frost depth measurements relative to thermistors wassite dependent averaging 0.1 cm at SB and 1.1 cm at SR, and was not significantly different than zero. Whenseparated by snow manipulation treatment at SR, overestimation of soil frost depth (5.5 cm) occurredon plots cleared of snow and underestimation (−1.5 cm) occurred on plots with snow. Despite somelimitations posed by site and surface suitability, GPR could be useful for adding a spatial component topre-installed soil frost monitoring networks

Taking the pulse of snowmelt: in situ sensors reveal seasonal, event and diurnal patterns of nitrate and dissolved organic matter variability in an upland forest stream

Highly resolved time series data are useful to accurately identify the timing, rate, and magnitude of solute transport in streams during hydrologically dynamic periods such as snowmelt. We used in situ optical sensors for nitrate (NO3 −) and chromophoric dissolved organic matter fluorescence (FDOM) to measure surface water concentrations at 30 min intervals over the snowmelt period (March 21–May 13, 2009) at a 40.5 hectare forested watershed at Sleepers River, Vermont. We also collected discrete samples for laboratory absorbance and fluorescence as well as δ18O–NO3 − isotopes to help interpret the drivers of variable NO3 − and FDOM concentrations measured in situ. In situ data revealed seasonal, event and diurnal patterns associated with hydrological and biogeochemical processes regulating stream NO3 − and FDOM concentrations. An observed decrease in NO3 − concentrations after peak snowmelt runoff and muted response to spring rainfall was consistent with the flushing of a limited supply of NO3 − (mainly from nitrification) from source areas in surficial soils. Stream FDOM concentrations were coupled with flow throughout the study period, suggesting a strong hydrologic control on DOM concentrations in the stream. However, higher FDOM concentrations per unit streamflow after snowmelt likely reflected a greater hydraulic connectivity of the stream to leachable DOM sources in upland soils. We also observed diurnal NO3 − variability of 1–2 μmol l−1 after snowpack ablation, presumably due to in-stream uptake prior to leafout. A comparison of NO3 − and dissolved organic carbon yields (DOC, measured by FDOM proxy) calculated from weekly discrete samples and in situ data sub-sampled daily resulted in small to moderate differences over the entire study period (−4 to 1% for NO3 − and −3 to −14% for DOC), but resulted in much larger differences for daily yields (−66 to +27% for NO3 − and −88 to +47% for DOC, respectively). Despite challenges inherent in in situ sensor deployments in harsh seasonal conditions, these data provide important insights into processes controlling NO3 − and FDOM in streams, and will be critical for evaluating the effects of climate change on snowmelt delivery to downstream ecosystems

In vitro simulation of torque-induced rotator cuff damage

Various aspects of rotator cuff tears have been studied in depth, including the primary pathogenesis and mechanical properties. There is, however, a lack of information available on the injury mechanics associated with sudden torque loading of the shoulder. To investigate the mechanical response of the Supraspinatus tendon and the joint capsule when exposed to repeated near-instantaneous torques, an in vitro test apparatus was developed. Supraspinatus and capsular reaction forces, capsular surface strains, and shoulder accelerations were measured over 30 cycles of applied torque. A decreasing logarithmic decay was found in the difference between the initial and final loads within each cycle. A generalized force-displacement fiber recruitment model was used to determine the protective role of the capsule by evaluating changes in stiffness. The results suggest that while relatively more damage happens in the first few high-torque load cycles, sudden adduction loading injuries are likely fatigue-based in nature

SafeCare®: Historical Perspective and Dynamic Development of an Evidence-Based Scaled-Up Model for the Prevention of Child Maltreatment

AbstractSafeCare is an evidence-based parent-training program that reduces child maltreatment, particularly neglect. The risk of child maltreatment, a public health issue affecting millions of U.S. children each year, can be markedly reduced by interventions such as SafeCare that deliver in-home services. Drawing from applied behavioral analysis roots, SafeCare focuses on providing parents with concrete skills in three areas: health, home safety, and parent-child/-infant interaction. This paper will include an overview of the SafeCare model, an historical perspective of its history and dynamic development, description of the theoretical underpinnings of the model, a description of the program targets and content by describing its modules and delivery, an overview of program outcomes, and data discussion of dissemination and implementation

Geographical variation in Hepatitis C-related severe liver disease and patient risk factors: A multicentre cross-sectional study

No abstract available

Spatial patterns of soil nitrification and nitrate export from forested headwaters in the northeastern United States

Nitrogen export from small forested watersheds is known to be affected by N deposition but with high regional variability. We studied 10 headwater catchments in the northeastern United States across a gradient of N deposition (5.4 - 9.4 kg ha-1 yr-1) to determine if soil nitrification rates could explain differences in stream water NO 3- export. Average annual export of two years (October 2002 through September 2004) varied from 0.1 kg NO3--N ha-1 yr-1 at Cone Pond watershed in New Hampshire to 5.1 kg ha-1 yr-1 at Buck Creek South in the western Adirondack Mountains of New York. Potential net nitrification rates and relative nitrification (fraction of inorganic N as NO3-) were measured in Oa or A soil horizons at 21-130 sampling points throughout each watershed. Stream NO3- export was positively related to nitrification rates (r2 = 0.34, p = 0.04) and the relative nitrification (r2 = 0.37, p = 0.04). These relationships were much improved by restricting consideration to the 6 watersheds with a higher number of rate measurements (59-130) taken in transects parallel to the streams (r 2 of 0.84 and 0.70 for the nitrification rate and relative nitrification, respectively). Potential nitrification rates were also a better predictor of NO3- export when data were limited to either the 6 sampling points closest to the watershed outlet (r2 = 0.75) or sampling points \u3c250 m from the watershed outlet (r2 = 0.68). The basal area of conifer species at the sampling plots was negatively related to NO3- export. These spatial relationships found here suggest a strong influence of near-stream and near-watershed-outlet soils on measured stream NO3- export. Copyright 2012 by the American Geophysical Union

Human Parainfluenza Virus Infection after Hematopoietic Stem Cell Transplantation: Risk Factors, Management, Mortality, and Changes over Time

Human parainfluenza viruses (HPIVs) are uncommon, yet high-risk pathogens after hematopoietic stem cell transplant (HCT). We evaluated 5178 pediatric and adult patients undergoing HCT between 1974 and 2010 to determine the incidence, risk factors, response to treatment, and outcome of HPIV infection as well as any change in frequency or character of HPIV infection over time. HPIV was identified in 173 patients (3.3%); type 3 was most common (66%). HPIV involved upper respiratory tract infection (URTI; 57%), lower respiratory tract infection (LRTI; 9%), and both areas of the respiratory tract (34%), at a median of 62 days after transplantation. In more recent years, HPIV has occurred later after HCT, whereas the proportion with nosocomial infection and mortality decreased. Over the last decade, HPIV was more common in older patients and in those receiving reduced intensity conditioning (RIC). RIC was a significant risk factor for later (beyond day +30). HPIV infections, and this association was strongest in patients with URTI. HCT using a matched unrelated donor (MURD), mismatched related donor (MMRD), age 10 to 19 years, and graft-versus-host disease (GVHD) were all risk factors for HPIV infections. LRTI, early (<30 days), age 10 to 19 years, MMRD, steroid use, and coinfection with other pathogens were risk factors for mortality. The survival of patients with LRTI, especially very early infections, was poor regardless of ribavirin treatment. HPIV incidence remains low, but may have delayed onset associated with RIC regimens and improving survival. Effective prophylaxis and treatment for HPIV are needed

The roles of calcium signaling and ERK1/2 phosphorylation in a Pax6(+/- )mouse model of epithelial wound-healing delay

BACKGROUND: Congenital aniridia caused by heterozygousity at the PAX6 locus is associated with ocular surface disease including keratopathy. It is not clear whether the keratopathy is a direct result of reduced PAX6 gene dosage in the cornea itself, or due to recurrent corneal trauma secondary to defects such as dry eye caused by loss of PAX6 in other tissues. We investigated the hypothesis that reducing Pax6 gene dosage leads to corneal wound-healing defects. and assayed the immediate molecular responses to wounding in wild-type and mutant corneal epithelial cells. RESULTS: Pax6(+/- )mouse corneal epithelia exhibited a 2-hour delay in their response to wounding, but subsequently the cells migrated normally to repair the wound. Both Pax6(+/+ )and Pax6(+/- )epithelia activated immediate wound-induced waves of intracellular calcium signaling. However, the intensity and speed of propagation of the calcium wave, mediated by release from intracellular stores, was reduced in Pax6(+/- )cells. Initiation and propagation of the calcium wave could be largely decoupled, and both phases of the calcium wave responses were required for wound healing. Wounded cells phosphorylated the extracellular signal-related kinases 1/2 (phospho-ERK1/2). ERK1/2 activation was shown to be required for rapid initiation of wound healing, but had only a minor effect on the rate of cell migration in a healing epithelial sheet. Addition of exogenous epidermal growth factor (EGF) to wounded Pax6(+/- )cells restored the calcium wave, increased ERK1/2 activation and restored the immediate healing response to wild-type levels. CONCLUSION: The study links Pax6 deficiency to a previously overlooked wound-healing delay. It demonstrates that defective calcium signaling in Pax6(+/- )cells underlies this delay, and shows that it can be pharmacologically corrected. ERK1/2 phosphorylation is required for the rapid initiation of wound healing. A model is presented whereby minor abrasions, which are quickly healed in normal corneas, transiently persist in aniridic patients, compromising the corneal stroma