344 research outputs found
Use of a Pressure Guidewire to Assess Pulmonary Artery Band Adequacy in the Hybrid Stage I Procedure for High‐risk Neonates with Hypoplastic Left Heart Syndrome and Variants
Objective The hybrid stage I procedure is an alternative palliative strategy for patients with hypoplastic left heart syndrome who traditionally have undergone the N orwood operation. At our institution, the hybrid stage I procedure is employed only for patients with high operative risk. Our objective was to describe our use of a pressure guidewire during the hybrid stage I procedure to assess quantitatively pulmonary artery band adequacy. Design After reviewing the charts on all high‐risk patients who underwent a hybrid stage I procedure at our institution, we compared two groups of patients: those who underwent the standard hybrid stage I palliation (standard cohort) and those with pressure wire‐facilitated assessment of distal branch pulmonary artery pressure (pressure wire cohort) to evaluate the impact of pressure guidewire use on procedural risk, radiation time, patient outcomes, and need for reoperation for pulmonary artery band adjustment. Results The pressure guidewire was used in 8 of 14 patients at the time of hybrid stage I procedure and was successful and without complication in all attempts. In the standard cohort, 67% of patients needed reoperation for pulmonary artery band adjustment, compared to 12.5% of patients in the pressure wire cohort ( P =.09). Procedure time, radiation exposure, and survival to hospital discharge were not different between groups. Conclusions This novel use of a pressure guidewire to assess quantitatively pulmonary artery band adequacy at the time of placement is feasible, safe and may decrease the need for reoperation for pulmonary artery band adjustment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97511/1/chd12005.pd
Outcomes of 1½- or 2-ventricle conversion for patients initially treated with single-ventricle palliation
ObjectiveAs outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere.MethodsNine patients (4 male patients) who had previously undergone the Fontan procedure (n = 3) or bidirectional cavopulmonary shunting (n = 6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n = 2), pulmonary arteriovenous malformation (n = 1), and preference for biventricular anatomy (n = 6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle–pulmonary artery conduit (Rastelli-type operation).ResultsFive patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169–352 minutes) and 129 minutes (range, 100–168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3–99.8 months), all survivors are in New York Heart Association class I.ConclusionsPatients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes
Hybrid approach for pulmonary atresia with intact ventricular septum: Early single center results and comparison to the standard surgical approach
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106725/1/ccd25181.pd
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Advancing Pharmacist Collaborative Care within Academic Health Systems.
INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system
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Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary β3-subunit.
Voltage-gated sodium channels comprise an ion-selective α-subunit and one or more associated β-subunits. The β3-subunit (encoded by the SCN3B gene) is an important physiological regulator of the heart-specific sodium channel, Nav1.5. We have previously shown that when expressed alone in HEK293F cells, the full-length β3-subunit forms trimers in the plasma membrane. We extend this result with biochemical assays and use the proximity ligation assay (PLA) to identify oligomeric β3-subunits, not just at the plasma membrane, but throughout the secretory pathway. We then investigate the corresponding clustering properties of the α-subunit and the effects upon these of the β3-subunits. The oligomeric status of the Nav1.5 α-subunit in vivo, with or without the β3-subunit, has not been previously investigated. Using super-resolution fluorescence imaging, we show that under conditions typically used in electrophysiological studies, the Nav1.5 α-subunit assembles on the plasma membrane of HEK293F cells into spatially localized clusters rather than individual and randomly dispersed molecules. Quantitative analysis indicates that the β3-subunit is not required for this clustering but β3 does significantly change the distribution of cluster sizes and nearest-neighbor distances between Nav1.5 α-subunits. However, when assayed by PLA, the β3-subunit increases the number of PLA-positive signals generated by anti-(Nav1.5 α-subunit) antibodies, mainly at the plasma membrane. Since PLA can be sensitive to the orientation of proteins within a cluster, we suggest that the β3-subunit introduces a significant change in the relative alignment of individual Nav1.5 α-subunits, but the clustering itself depends on other factors. We also show that these structural and higher-order changes induced by the β3-subunit do not alter the degree of electrophysiological gating cooperativity between Nav1.5 α-subunits. Our data provide new insights into the role of the β3-subunit and the supramolecular organization of sodium channels, in an important model cell system that is widely used to study Nav channel behavior.We would like to thank the Gurdon Institute Imaging Facility
for use of their microscope and general assistance. This
work was supported by a British Heart Foundation grant
(PG/14/79/31102) to APJ and CLHH, The Wellcome Trust,
award number: 105727/Z/14/Z to CLHH and a Medical
Research Council grant (MR/K015591/1) to CLF, RAL, and
STFC
Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate
Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Étude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations
Ca. Nitrososphaera and Bradyrhizobium are inversely correlated and related to agricultural practices in long-term field experiments
Agricultural land management, such as fertilization, liming, and tillage affects soil properties, including pH, organic matter content, nitrification rates, and the microbial community. Three different study sites were used to identify microorganisms that correlate with agricultural land use and to determine which factors regulate the relative abundance of the microbial signatures of the agricultural land-use. The three sites included in this study are the Broadbalk Experiment at Rothamsted Research, UK, the Everglades Agricultural Area, Florida, USA, and the Kellogg Biological Station, Michigan, USA. The effects of agricultural management on the abundance and diversity of bacteria and archaea were determined using high throughput, barcoded 16S rRNA sequencing. In addition, the relative abundance of these organisms was correlated with soil features. Two groups of microorganisms involved in nitrogen cycle were highly correlated with land use at all three sites. The ammonia oxidizing-archaea, dominated by Ca. Nitrososphaera, were positively correlated with agriculture while a ubiquitous group of soil bacteria closely related to the diazotrophic symbiont, Bradyrhizobium, was negatively correlated with agricultural management. Analysis of successional plots showed that the abundance of ammonia oxidizing-archaea declined and the abundance of bradyrhizobia increased with time away from agriculture. This observation suggests that the effect of agriculture on the relative abundance of these genera is reversible. Soil pH and NH(3) concentrations were positively correlated with archaeal abundance but negatively correlated with the abundance of Bradyrhizobium. The high correlations of Ca. Nitrososphaera and Bradyrhizobium abundances with agricultural management at three long-term experiments with different edaphoclimatic conditions allowed us to suggest these two genera as signature microorganisms for agricultural land use
The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU
We present a statistical analysis of the first 300 stars observed by the
Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six
detected planets and three brown dwarfs; from these detections and our contrast
curves we infer the underlying distributions of substellar companions with
respect to their mass, semi-major axis, and host stellar mass. We uncover a
strong correlation between planet occurrence rate and host star mass, with
stars M 1.5 more likely to host planets with masses between 2-13
M and semi-major axes of 3-100 au at 99.92% confidence. We fit a
double power-law model in planet mass (m) and semi-major axis (a) for planet
populations around high-mass stars (M 1.5M) of the form , finding = -2.4 0.8 and
= -2.0 0.5, and an integrated occurrence rate of %
between 5-13 M and 10-100 au. A significantly lower occurrence rate
is obtained for brown dwarfs around all stars, with 0.8% of
stars hosting a brown dwarf companion between 13-80 M and 10-100
au. Brown dwarfs also appear to be distributed differently in mass and
semi-major axis compared to giant planets; whereas giant planets follow a
bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs
exhibit just the opposite behaviors. Comparing to studies of short-period giant
planets from the RV method, our results are consistent with a peak in
occurrence of giant planets between ~1-10 au. We discuss how these trends,
including the preference of giant planets for high-mass host stars, point to
formation of giant planets by core/pebble accretion, and formation of brown
dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres
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