Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer ...(RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen.
A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks.
Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each).
Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Myofascial release techniques at the time of complex hernia repair allow for tension-free closure of the midline fascia. Two common techniques are the open external oblique release (EOR) and ...the transversus abdominis release (TAR). Each technique has its reported advantages and disadvantages, but there have been few comparative studies. The purpose of this project was to compare the outcomes of these two myofascial release techniques.
Methods
The Americas Hernia Society Quality Collaborative (AHSQC) database was queried and produced a data set on 24 May 2018. All patients undergoing open incision hernia repair with an open EOR or TAR were evaluated, and outcomes were compared including hernia recurrence, quality of life, and 30-day wound-related complications.
Results
3610 patients met the inclusion criteria of undergoing open incisional hernia repair (501 undergoing EOR and 3109 undergoing TAR). Seventy surgeons from 50 institutions contributed EOR patients, and 124 surgeons from 89 institutions contributed TAR patients with no differences between the two groups in surgeons’ affiliation. Comparing open EOR and TAR showed no significant differences in hernia recurrence, quality of life, or 30-day surgical site infection rate. EOR had a significantly higher rate of surgical site occurrences compared with TAR (
p
< 0.05); however, this did not result in an increase in surgical site occurrences requiring procedural interventions.
Conclusions
Equivalent outcomes were achieved using the EOR or TAR techniques in the open repair of incisional hernias. Both techniques offer consistently good outcomes and are important adjuncts in the repair of complex incisional hernias.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The design and development process for the Square Kilometre Array (SKA) radio telescope, the Low Frequency Aperture Array component, was progressed during the SKA pre-construction phase by an ...international consortium, with the goal of meeting requirements for a critical design review. As part of the development process a full-sized prototype SKA Low station was deployed, the Aperture Array Verification System 1 (AAVS1). We provide a system overview and describe the commissioning results of AAVS1, which is a low frequency radio telescope with 256 dual-polarisation log-periodic dipole antennas working as a phased array. A detailed system description is provided, including an in-depth overview of relevant sub-systems, ranging from hardware, firmware, software, calibration,and control sub-systems. Early commissioning results cover initial bootstrapping, array calibration, stability testing, beam-forming,and on-sky sensitivity validation. Lessons learned are presented, along with future developments.
A laboratory-based study of the performance of a floor-based task ventilation system designed for use in office buildings has been completed. With the task ventilation system, occupants can adjust ...the flow rate and direction of air supplied to their work space through floor-mounted supply grilles. Air exits the ventilated space through a ceiling-mounted return grille. To study indoor airflow patterns, the age of air at multiple indoor locations was measured using the tracer gas step-up procedure. To study the intra-room transport of tobacco smoke particles, cigarettes were smoked mechanically in one workstation and particle concentrations were measured at multiple indoor locations. Test variables included supply flow rates, temperatures, supply directions, and internal heat loads. Multiple floor supply units were in operation simultaneously. During all tests, the ventilation system supplied 100% outside air. Our major findings are as follows. (1) Deviations from a uniform age of air, and a uniform particle concentration, were generally less than 30%. (2) With two floor-supply units operating and supply air directed toward the occupant, the age of air in the breathing zone was about 20–40% less than the age of air that would occur in the room if the air was perfectly mixed. (3) With two floor-supply units operating, the air appears to travel from the floor to the ceiling in a piston-like flow pattern. (4) With three floor-supply units operating, a two-zone flow pattern, with a piston-like flow in the lower region of the room and mixing in the upper region, was evident at some operating conditions. (5) A strong (
r
2 = 0.81) correlation was found between the rate of change in the average age of air with height and two factors hypothesized to be determinants of the indoor airflow pattern. (6) Workstations without a cigarette smoking machine and with an operating task ventilation system were not significantly protected from tobacco smoke in an adjacent workstation.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
It is important to understand health-risk behaviours among young adults, as modifications in this can enhance and lessen the risk of chronic illness later in life. The purpose of the current study ...was to determine the prevalence of a broad range of health-risk behaviours among post-secondary students from across Canada, and to determine whether institutional variability exists in the prevalence of these behaviours.
Data were collected from 8,182 undergraduate students enrolled in one of eight Canadian post-secondary institutions during the fall or spring of 2009, using the National College Health Assessment (NCHA). The NCHA consists of 60 questions, assessing student health status and engagement in various health behaviours.
Findings show relatively low prevalence in smoking (13.1%) marijuana (17.5%) or other illicit drug use (3.5%), and risky sexual behaviour (12%). Binge drinking, however, was much higher, with nearly 60% of students consuming more than 5 alcoholic drinks in a single occasion during the past 15 days. Similarly, prevalence rates for physical inactivity (72.2%), inadequate sleep (75.6%) and low fruit and vegetable intake (88.0%) were all high among the student population. Results also found that students in smaller institutions exhibited higher rates of inactivity, binge drinking, and marijuana and illicit drug use compared to institutions having a larger student body.
Overall, findings point to the need for more concentrated health promotion campaigns, specifically targeting sleep, fruit and vegetables intake, and greater participation in physical activity. Given evidence of some institutional variability, future efforts are warranted in exploring how best to increase institutional commitment for collecting surveillance data on Canadian post-secondary students.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite continuing improvement in myocardial protection and surgical technique, the repair of complex congenital heart lesions can result in cardiopulmonary compromise refractory to conventional ...therapy. In a 29-month period, 24 patients (aged 14 hours to 6 years) were treated with extracorporeal membrane oxygenation (ECMO) 28 times for profound cardiopulmonary failure. Four patients required ECMO after each of two cardiopulmonary bypass procedures. Seventeen patients required ECMO to be initiated in the operating room: 12 (71%) were weaned successfully from ECMO, and 8 (47%) survived. Seven patients had ECMO initiated in the intensive care unit: 6 (86%) were weaned, and 5 (71%) survived. Serial echocardiograms demonstrated substantial recovery of cardiac function in 18 of 21 instances (86%) of ventricular failure from myocardial dysfunction. Overall, 18 of 24 patients (75%) were successfully weaned from ECMO including all 4 who underwent 2 ECMO treatments. We conclude that ECMO can successfully salvage children who have serious cardiopulmonary failure immediately after a congenital heart operation and that long-term survival is possible after two ECMO treatments.
Many nutrition models rely on summative equations to estimate feed and diet energy concentrations. These models partition feed into nutrient fractions and multiply the fractions by their estimated ...true digestibility, and the digestible mass provided by each fraction is then summed and converted to an energy value. Nonfiber carbohydrate (NFC) is used in many models. Although it behaves as a nutritionally uniform fraction, it is a heterogeneous mixture of components. To reduce the heterogeneity, we partitioned NFC into starch and residual organic matter (ROM), which is calculated as 100 − CP − LCFA − ash − starch – NDF, where crude protein (CP), long-chain fatty acids (LCFA), ash, starch, and neutral detergent fiber (NDF) are a percentage of DM. However, the true digestibility of ROM is unknown, and because NDF is contaminated with both ash and CP, those components are subtracted twice. The effect of ash and CP contamination of NDF on in vivo digestibility of NDF and ROM was evaluated using data from 2 total-collection digestibility experiments using lactating dairy cows. Digestibility of NDF was greater when it was corrected for ash and CP than without correction. Conversely, ROM apparent digestibility decreased when NDF was corrected for contamination. Although correcting for contamination statistically increased NDF digestibility, the effect was small; the average increase was 3.4%. The decrease in ROM digestibility was 7.4%. True digestibility of ROM is needed to incorporate ROM into summative equations. Data from multiple digestibility experiments (38 diets) using dairy cows were collated, and ROM concentrations were regressed on concentration of digestible ROM (ROM was calculated without adjusting for ash and CP contamination). The estimated true digestibility coefficient of ROM was 0.96 (SE = 0.021), and metabolic fecal ROM was 3.43 g/100 g of dry matter intake (SE = 0.30). Using a smaller data set (7 diets), estimated true digestibility of ROM when calculated using NDF corrected for ash and CP contamination was 0.87 (SE = 0.025), and metabolic fecal ROM was 3.76 g/100 g (SE = 0.60). Regardless of NDF method, ROM exhibited nutritional uniformity. The ROM fraction also had lower errors associated with the estimated true digestibility and its metabolic fecal fraction than did NFC. Therefore, ROM may result in more accurate estimates of available energy if integrated into models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This trial tested whether intensive blood-pressure control retards the progression of chronic kidney disease in black patients with hypertension. Although there was an apparent benefit among patients ...with baseline proteinuria (urinary protein-to-creatinine ratio, >0.22), those with a normal protein-to-creatinine ratio had no benefit. Among all patients, intensive blood-pressure control had no effect on disease progression.
Chronic kidney disease is a major public health problem. In national surveys, the prevalence of chronic kidney disease (stages 1 through 4) among adults in the United States increased from 10% during the period from 1988 through 1994 to 13% during the period from 1999 through 2004.
1
In 2006, the cost to the federal government for the treatment of end-stage renal disease (ESRD) was $23 billion, and the corresponding treatment cost for chronic kidney disease was $49 billion.
2
In the United States, approximately 30% of incident ESRD cases are attributed to hypertension.
2
The burden of hypertension-related chronic kidney disease and . . .
Appropriate trace mineral supplementation can improve immune response and hoof health in cattle and at much higher rates of supplementation to swine and poultry can alter microbial colonization of ...the gut, resulting in improved gut health. Diet can influence fecal microbial excretion in cattle, and the fecal microbiome may serve as a means for assessing gastrointestinal microbial changes. We hypothesized that feeding diets that differed in source of supplemental Cu, Zn, or Mn would alter the relative abundance of fecal microbes in lactating dairy cattle and that organic Zn would have the greatest effect. Twenty-four cows were fed diets devoid of supplemental Cu, Zn, and Mn for a 16-d preliminary phase (basal diet provided 9, 29, and 32 mg/kg of Cu, Zn, and Mn, respectively), and then were randomly assigned to 1 of 3 treatment diets (n = 8 cows/treatment): one group of cows was fed supplemental Cu, Zn, and Mn from sulfate minerals; the second group was fed glycinate minerals; and the third group was fed Cu and Mn sulfate with glycinate Zn. Assayed total dietary concentrations were approximately 21, 73, and 72 mg/kg for Cu, Zn, and Mn, respectively. Milk production (averaged 38.8 kg/d), DMI (averaged 25.8 kg/d), and milk components were not affected by treatment. Fecal DNA was extracted, amplified using a universal primer targeting the V4-V5 hypervariable region of the 16S rRNA gene, and sequenced to compare microbial community composition between treatments. Relative abundances of Treponema species-level operational taxonomic units (OTU) were less for animals fed Cu and Mn sulfate with glycinate Zn compared with sulfates alone, but were similar to animals fed glycinate mineral sources. Relative abundances for exclusive glycinate mineral and sulfate mineral treatments were similar. Treponema OTU and cultured representatives are often associated with bovine digital dermatitis. These data may provide an additional link between organic Zn supplementation and improved hoof health. To our knowledge this is the first report of a dietary treatment decreasing the relative abundance of Treponema OTU in cattle feces; however, the potential benefits of this response on overall animal health and the mechanism for the observed responses are unknown and warrant further investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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