Field Trial Performance of Herculex XTRA (Cry34Ab1/Cry35Ab1) and SmartStax (Cry34Ab1/Cry35Ab1 + Cry3Bb1) Hybrids and Soil Insecticides Against Western and Northern Corn Rootworms (Coleoptera: Chrysomelidae).

Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), and northern corn rootworm, Diabrotica barberi Smith and Lawrence (Coleoptera: Chrysomelidae), are important insect pests in corn, Zea mays L. For more than a decade, growers have been using transgenic plants expressing proteins from the bacterium Bacillus thuringiensis (Bt) to protect corn roots from feeding. In 2011, western corn rootworm populations were reported to have developed resistance to Bt hybrids expressing Cry3Bb1 and later found to be cross-resistant to hybrids expressing mCry3A and eCry3.1Ab. The identification of resistance to Cry3 (Cry3Bb1, mCry3A, and eCry3.1Ab) hybrids led to concerns about durability and efficacy of products with single traits and of products containing a pyramid of a Cry3 protein and the binary Bt proteins Cry34Ab1 and Cry35Ab1. From 2012 to 2014, 43 field trials were conducted across the central United States to estimate root protection provided by plants expressing Cry34Ab1/Cry35Ab1 alone (Herculex RW) or pyramided with Cry3Bb1 (SmartStax). These technologies were evaluated with and without soil-applied insecticides to determine if additional management measures provided benefit where Cry3 performance was reduced. Trials were categorized for analysis based on rootworm damage levels on Cry3-expressing hybrids and rootworm feeding pressure within each trial. Across scenarios, Cry34Ab1/Cry35Ab1 hybrids provided excellent root protection. Pyramided traits provided greater root and yield protection than non-Bt plus a soil-applied insecticide, and only in trials where larval feeding pressure exceeded two nodes of damage did Cry34Ab1/Cry35Ab1 single-trait hybrids and pyramided hybrids show greater root protection from the addition of soil-applied insecticides.

Evaluation of forage soybean, with and without pearl millet, as an alternative for beef replacement heifers.

Apparent ruminal digestibility of forage soybean-based silages, with and without pearl millet, was determined along with evaluation of silages on heifer performance and reproductive function. Fermenters were utilized in a Latin square design and randomly assigned to 1 of the following treatments: 1) control diet of alfalfa haylage (CON), 2) soybean silage (SB) or 3) soybean and pearl millet silage (SB×PM). All diets were formulated to meet or exceed nutrient requirements of replacement beef heifers targeted to gain 0.79 kg/d. These same diets were fed to 90 Angus-Simmental beef replacement heifers [body weight (BW) = 366 kg; body condition score (BCS) = 5.53; age = 377 ± 11 d] 65 d prior to timed artificial insemination (TAI). Heifers were randomly allotted by breed, BCS and BW to 1 of the 3 treatments, with 3 reps/treatment. Diets were terminated 21 d post-TAI and heifers were commingled and placed on a common diet. Pubertal status was determined by progesterone concentrations of 2 blood samples taken 10 d apart prior to both trial initiation as well as initiation of estrous synchronization. Ovulatory follicle diameter was determined at time of breeding by ultrasonography. Pregnancy diagnosis was accomplished 35 and 66 d post-TAI, respectively, to calculate TAI and end of season pregnancy rates. Neither SB nor SB×PM had an effect (P > 0.37) on apparent ruminal digestion of nutrients compared to the CON. Final BW (414 kg; P ≥ 0.10) and BCS (5.28; P ≥ 0.26) for the heifers were similar among treatments. Likewise, there were no differences in TAI (48%; P > 0.43) or overall breeding season (93%; P > 0.99) pregnancy rates. Ovulatory follicle diameters (11.7 mm) was not different (P > 0.19) among treatments. In summary, forage soybean-based silages, with and without pearl millet, was an acceptable alternative forage for developing replacement beef heifers.

The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.

Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of a GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multiprotein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This chapter reviews the structure/function of E-box-GATA composite cis-elements, which collectively constitute an important sector of the hematopoietic stem and progenitor cell cistrome.

Navigating Transcriptional Coregulator Ensembles to Establish Genetic Networks: A GATA Factor Perspective.

Complex developmental programs require orchestration of intrinsic and extrinsic signals to control cell proliferation, differentiation, and survival. Master regulatory transcription factors are vital components of the machinery that transduce these stimuli into cellular responses. This is exemplified by the GATA family of transcription factors that establish cell type-specific genetic networks and control the development and homeostasis of systems including blood, vascular, adipose, and cardiac. Dysregulated GATA factor activity/expression underlies anemia, immunodeficiency, myelodysplastic syndrome, and leukemia. Parameters governing the capacity of a GATA factor expressed in multiple cell types to generate cell type-specific transcriptomes include selective coregulator usage and target gene-specific chromatin states. As knowledge of GATA-1 mechanisms in erythroid cells constitutes a solid foundation, we will focus predominantly on GATA-1, while highlighting principles that can be extrapolated to other master regulators. GATA-1 interacts with ubiquitous and lineage-restricted transcription factors, chromatin modifying/remodeling enzymes, and other coregulators to activate or repress transcription and to maintain preexisting transcriptional states. Major unresolved issues include: how does a GATA factor selectively utilize diverse coregulators; do distinct epigenetic landscapes and nuclear microenvironments of target genes dictate coregulator requirements; and do gene cohorts controlled by a common coregulator ensemble function in common pathways. This review will consider these issues in the context of GATA factor-regulated hematopoiesis and from a broader perspective.

Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with chopped whole plant corn on heifer growth performance and diet digestibility in beef cattle.

Two experiments were conducted to evaluate the effect of feeding corn modified wet distillers grain plus solubles (MWDGS; 48% DM) co-ensiled with chopped whole plant corn (WC) on growth performance, dietary intake, and nutrient digestibility of beef cattle. In Exp. 1, 96 Angus-crossed heifers (2 yr old; 522 ± 49.1 kg BW; 5.3 ± 0.1 BCS) were stratified and blocked according to BW and stratified by BCS in each block in a randomized complete block design (24 pens; 4 heifers/pen; 6 treatment replications). Groups were assigned to 1 of 4 dietary treatments for a 62 d trial. Treatments were 1) corn silage (CS) and soybean meal (CON), 2) MWDGS co-ensiled with chopped whole plant corn (WC; CO-EN), 3) CS mixed with MWDGS at feeding (CS+WDG), and 4) CS mixed with dry distillers grain plus solubles (DDGS) at feeding (CS+DDG). In Exp. 2, 4 crossbred beef steers (initial BW = 278 ± 18 kg) fitted with permanent ruminal cannulas were used in a balanced 4 × 4 Latin square to test the effects of feeding MWDGS co-ensiled with WC on DM intake, ruminal fermentation characteristics, and total tract digestibility. There were four 14-d periods, with 10 d for diet adaptation and 4 d for samples collection. Orthogonal contrasts were used and compared CON vs. diets containing distillers grains (DGD), CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and CS+WDG vs. CS+DDG. In Exp. 1, the CON fed heifers resulted in greater G:F (P = 0.04) compared with those fed DGD. However, ADG (P = 0.03), final BW (P = 0.04), and BW gain (P = 0.03) were greatest for DGD diets compared with CON and greatest (P = 0.04) for CO-EN when compared with MIX. Apart from a slightly greater acetate concentration (P = 0.05), which resulted in a greater acetate to propionate ratio (P = 0.03) for the CON diet compared with DGD, no important differences were observed on intake, diet digestibility, or fermentation characteristics when comparing the CON treatment with DGD or when comparing CS+WDG with CS+DDG. However, the CO-EN diet resulted in decreased DMI (P = 0.05) and consequently decreased OM (P = 0.05), N (P = 0.04), and NDF (P = 0.02) intakes compared with MIX. Data from these studies suggest that MWDGS co-ensiled with WC can successfully replace traditional corn-based diets supplemented with soybean meal and corn silage diets supplemented with distillers grains without compromising digestibility and growth performance in pregnant heifers.

Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with direct-cut forage on feedlot performance, carcass characteristics, and diet digestibility of finishing steers.

Two experiments were conducted to evaluate the effects of feeding corn modified wet distillers grain plus solubles (MWDGS) co-ensiled with direct-cut forage (DC) to beef steers, on feedlot performance and total tract digestibility. In Exp. 1, sixty-four crossbred Angus steers (n = 64; 329 ± 43 kg) were blocked by BW and randomly assigned to 1 of 4 dietary treatments: 1) corn-silage and soybean meal (CON), 2) DC co-ensiled with MWDGS (CO-EN), 3) haylage mixed with MWDGS at feeding (H+WDG), and 4) haylage mixed with dry distillers grains plus solubles at feeding (H+DDG). Steers were harvested when they reached an endpoint of 1.1 cm of 12th-rib back fat. In Exp. 2, four ruminally cannulated beef steers (initial BW = 556 ± 31 kg) were used in a 4 × 4 Latin square to evaluate digestibility of diets used in Exp. 1. Experimental periods were 14 d in length with 10 d for diet adaptation and 4 d for sample collection. Three linear orthogonal contrasts were used to compare effects of 1) CON vs. diets containing distillers grains (DGD), 2) CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and 3) H+WDG vs. H+DDG. In Exp. 1, DMI was less (P < 0.001) for steers fed CON compared with those fed DGD and greatest (P < 0.001) for steers fed CO-EN compared with MIX. Corn-silage- and soybean-meal-fed steers had more days on feed than those fed DGD (P = 0.001). Body weight gain (P = 0.02) was greater for CO-EN compared with MIX. Fat thickness at the 12th and 13th ribs was greater (P = 0.03) for DGD steers compared with CON steers. Hot carcass weight was greater (P = 0.03) for steers fed CO-EN compared with those fed MIX. Steers fed CON resulted in greater marbling scores (P = 0.01) compared DGD-fed steers. Longissimus muscle area was greater (P = 0.01) for CON-fed steers compared with all other treatments. In Exp. 2, no differences (P > 0.10) in DM, OM, or N intakes were observed. Apparent total tract DM (P = 0.01) and N (P = 0.02) digestibility were greatest in steers fed CON compared with all others. Steers fed DGD had less (P = 0.02) rumen NH(3) concentrations compared with CON. The CON diet resulted in greater molar concentrations of VFA (P = 0.03) and decreased acetate to propionate ratio (P = 0.03) compared with all DGD. These data suggest that feeding MWDGS co-ensiled with direct-cut forage results in reduced diet digestibility but equal or greater feedlot performance and similar carcass and characteristics when compared with a corn diet supplemented with soybean meal and diets where MWDGS and DDGS were added at the mixer.

Assessment of boreal forest historical C dynamics in the Yukon River Basin: relative roles of warming and fire regime change.

Carbon (C) dynamics of boreal forest ecosystems have substantial implications for efforts to mitigate the rise of atmospheric CO2 and may be substantially influenced by warming and changing wildfire regimes. In this study we applied a large-scale ecosystem model that included dynamics of organic soil horizons and soil organic matter characteristics of multiple pools to assess forest C stock changes of the Yukon River Basin (YRB) in Alaska, USA, and Canada from 1960 through 2006, a period characterized by substantial climate warming and increases in wildfire. The model was calibrated for major forests with data from long-term research sites and evaluated using a forest inventory database. The regional assessment indicates that forest vegetation C storage increased by 46 Tg C, but that total soil C storage did not change appreciably during this period. However, further analysis suggests that C has been continuously lost from the mineral soil horizon since warming began in the 1970s, but has increased in the amorphous organic soil horizon. Based on a factorial experiment, soil C stocks would have increased by 158 Tg C if the YRB had not undergone warming and changes in fire regime. The analysis also identified that warming and changes in fire regime were approximately equivalent in their effects on soil C storage, and interactions between these two suggests that the loss of organic horizon thickness associated with increases in wildfire made deeper soil C stocks more vulnerable to loss via decomposition. Subbasin analyses indicate that C stock changes were primarily sensitive to the fraction of burned forest area within each subbasin and that boreal forest ecosystems in the YRB are currently transitioning from being sinks to sources at -0.7% annual area burned. We conclude that it is important for international mitigation efforts focused on controlling atmospheric CO2 to consider how climate warming and changes in fire regime may concurrently affect the CO2 sink strength of boreal forests. It is also important for large-scale biogeochemical and earth system models to include organic soil dynamics in applications to assess regional C dynamics of boreal forests responding to warming and changes in fire regime.

Economic threshold for soybean aphid (Hemiptera: Aphididae).

Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), reached damaging levels in 2003 and 2005 in soybean, Glycine max (L.) Merrill, in most northern U.S. states and Canadian provinces, and it has become one of the most important pests of soybean throughout the North Central region. A common experimental protocol was adopted by participants in six states who provided data from 19 yield-loss experiments conducted over a 3-yr period. Population doubling times for field populations of soybean aphid averaged 6.8 d +/- 0.8 d (mean +/- SEM). The average economic threshold (ET) over all control costs, market values, and yield was 273 +/- 38 (mean +/- 95% confidence interval [CI], range 111-567) aphids per plant. This ET provides a 7-d lead time before aphid populations are expected to exceed the economic injury level (EIL) of 674 +/- 95 (mean +/- 95% CI, range 275-1,399) aphids per plant. Peak aphid density in 18 of the 19 location-years occurred during soybean growth stages R3 (beginning pod formation) to R5 (full size pod) with a single data set having aphid populations peaking at R6 (full size green seed). The ET developed here is strongly supported through soybean growth stage R5. Setting an ET at lower aphid densities increases the risk to producers by treating an aphid population that is growing too slowly to exceed the EIL in 7 d, eliminates generalist predators, and exposes a larger portion of the soybean aphid population to selection by insecticides, which could lead to development of insecticide resistance.

Primary hyperaldosteronism in a dog with concurrent lymphoma.

An 11-year-old, male castrated English springer spaniel was presented for muscle weakness, lethargy and anorexia while undergoing treatment of Stage IV lymphoma. Persistent hypokalemia prompted multiple diagnostic tests. Serum aldosterone levels, surgical exploration and histopathology confirmed primary hyperaldosteronism. Hyperaldosteronism is a rarely reported endocrinopathy in the dog. This report describes a case in which immunohistochemistry was utilized to confirm the diagnosis of an aldosterone-secreting tumour.

Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter.

Histone acetylation precedes activation of many genes. However, the establishment and consequences of long-range acetylation patterns are poorly understood. To define molecular determinants of the developmentally dynamic histone acetylation pattern of the beta-globin locus, we compared acetylation of the locus in MEL and CB3 erythroleukemia cells. CB3 cells lack the beta-globin locus control region (LCR) binding protein p45/NF-E2. We found that p45/NF-E2 was required for histone hyperacetylation at adult beta-globin promoters approximately 50 kilobases downstream of the LCR, but not at the LCR. Surprisingly, RNA polymerase II associated with the LCR in a p45/NF-E2-independent manner, while its recruitment to the promoter required p45/NF-E2. We propose that polymerase accesses the LCR and p45/NF-E2 induces long-range transfer of polymerase to the promoter, resulting in transcriptional activation.

"Floating knee" injuries: ipsilateral fractures of the femur and tibia.

Ipsilateral fractures of the femur and tibia have been called "floating knee" injuries and may include combinations of diaphyseal, metaphyseal, and intra-articular fractures. These are often high-energy injuries and most frequently occur in the polytrauma patient. Many of these fractures are open, with associated vascular injuries. Surgical stabilization of both fractures and early mobilization of the patient and the extremity produce the best clinical outcomes. The use of a radiolucent operating room table and the introduction of retrograde intramedullary fixation of femoral fractures have facilitated surgical stabilization of some floating-knee fracture patterns. Although treatment planning for each fracture in the extremity should be considered individually to achieve the optimal result, the effect of that decision must be considered in light of the overall injury status of the entire extremity. Collateral ligament and meniscal injuries may also be associated with this fracture complex. Complications (such as compartment syndrome, loss of knee motion, failure to diagnose knee ligament injury, and the need for amputation) are not infrequent. Better results and fewer complications are observed when both fractures are diaphyseal than when one or both are intra-articular.

Vagus nerve stimulation and drug reduction.

The authors prospectively assessed drug reduction and patient satisfaction in 21 patients using vagus nerve stimulation (VNS) for refractory epilepsy and compared results to a case-matched control group with a mean follow-up of 13.2 months. Significant antiepileptic drug (AED) reduction occurred in 9/21 (42.9%) of VNS patients averaging 0.43 AED/patient, with dose reduction in four patients (19.0%). For 12/21 (57.1%) patients not reducing AED, dose reduction occurred in 6/21 (28.6%). Drug and dose reduction of AED is possible in patients using VNS for refractory epilepsy without loss of seizure control and with improved patient satisfaction.

Growth factor modulation of distraction osteogenesis in a segmental defect model.

A model was established in 39 dogs to investigate the growth factor modulation of regenerate bone in distraction osteogenesis. A segment of the diaphysis of the radius was resected unilaterally. An osteotomy was made proximal to the segmental defect to create a transport segment. A monolateral external fixator was applied. After a latency period, the segment was transported across the defect. One week after the transport assembly contacted the distal pin clamp, an ipsilateral osteotomy of the proximal ulna was performed. In 20 dogs, transforming growth factor-beta was injected into the regenerate bone halfway through the transport period. Four dogs were sacrificed before docking, when the regenerate bone was still immature. In specimens harvested halfway through the transport period, evidence was found of intramembranous ossification during distraction. In specimens harvested after the transport assembly contacted the distal pin clamp, evidence was found that the mature regenerate formed by endochondral ossification. Therefore, a combined mechanism of ossification is proposed for this segmental defect model that includes mechanical stimulus for bone differentiation. The one-time administration of transforming growth factor-beta retarded the formation of a stable, united regenerate. It is concluded that transforming growth factor-beta caused an effect opposite to that which was desired.

Effect of immediate weightbearing on plated fractures of the humeral shaft.

BACKGROUND: This study evaluated the effect of immediate weightbearing on fractures of the humeral shaft treated with dynamic compression plates. METHODS: Eighty-three fractures met the inclusion criteria. The weightbearing status of the humerus was based on associated injuries and not the fracture pattern. There were no differences between the weightbearing and nonweightbearing groups in patient or fracture demographics. RESULTS: Ninety-four percent of the fractures healed after the initial operation. Two in the nonweightbearing group and three in the weightbearing group required a second operation to achieve union. Alignment did not differ between the two groups. Immediate full weight. bearing had no effect on the union or malunion rate. CONCLUSION: When indicated, open reduction and internal fixation of the diaphysis of the humerus, followed by immediate weightbearing through the involved humerus, is a safe and efficacious procedure.

A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is essential for Caenorhabditis elegans embryogenesis.

The highly conserved ubiquitin/proteasome pathway controls the degradation of many critical regulatory proteins. Proteins are posttranslationally conjugated to ubiquitin through a concerted set of reactions involving activating (E1), conjugating (E2), and ligase (E3) enzymes. Ubiquitination targets proteins for proteolysis via the proteasome and may regulate protein function independent of proteolysis. We describe the cloning and functional analysis of new members of the HECT domain family of E3 ubiquitin ligases. Murine Wwp1 encoded a broadly expressed protein containing a C2 domain, four WW domains, and a catalytic HECT domain. A Caenorhabditis elegans gene was cloned encoding a HECT domain protein (CeWWP1), which was highly homologous to murine and human WWP1. Disruption of CeWwp1 via RNA interference yielded an embryonic lethal phenotype, despite the presence of at least six additional C. elegans genes encoding HECT domain proteins. The embryonic lethality was characterized by grossly abnormal morphogenesis during late embryogenesis, despite normal proliferation early in embryogenesis. CeWWP1 must therefore have unique and nonredundant functions critical for embryogenesis.

Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model.

A study was performed in dogs to evaluate the dose-response characteristics and effectiveness of recombinant human bone morphogenetic protein-2 with a collagen sponge carrier in a segmental defect model. Twenty-seven dogs underwent bilateral radial osteotomies with creation of a 2.5-cm diaphyseal defect. All received autogenous cancellous bone graft in one defect and a collagen implant in the other. These implants contained recombinant human bone morphogenetic protein-2 at the following doses: group 1 at 0 microg (three dogs, 0 microg/ml total implant volume), group 2 at 150 microg (three dogs, 50 microg/ml), group 3 at 600 ,g (three dogs, 200 microg/ml), group 4 at 2,400 microg (three dogs, 800 microg/ml), group 5 at 0 microg (five dogs, 0 microg/ml), group 6 at 150 microg (five dogs, 200 microg/ml), and group 7 at 600 microg (five dogs, 50 microg/ml). The defects were stabilized with external fixators. The dogs in groups 1-4 were killed at 12 weeks postoperatively, and those in groups 5-7 were killed at 24 weeks postoperatively except for one dog in group 7, which was killed at 48 weeks. Evaluation included monthly radiographs, biomechanical testing, and nondemineralized histology. All 27 radii with autogenous cancellous bone graft and all 19 implants treated with recombinant human bone morphogenetic protein-2 achieved radiographic and histologic union and gross stability. The eight radii treated with collagen carrier alone went on to radiographic and histologic nonunion and were grossly unstable at death. A dose-dependent occurrence of cyst-like bone voids was noted radiographically and histologically. Biomechanical performance tended to be better at the lowest dose studied at 12 weeks, and all three doses performed better than the placebo (p < 0.05) at 12 and 24 weeks. By 24 weeks, radiolucent areas corresponding to histologic bone voids persisted radiographically, although there was evidence of early bone remodeling. This remodeling progressed to 48 weeks in the single animal followed to this time point, although bone voids remained. These radiologic findings were confirmed histologically. Recombinant human bone morphogenetic protein-2 in a collagen sponge carrier has significant osteoinductive activity in this canine segmental defect model. A dose-response relationship is evident, with heterotopic bone and cyst-like void formation at higher doses and a minimum effective dose of 0-150 microg. At 12 and 24 weeks postoperatively, biomechanical parameters achieved by defects treated with recombinant human bone morphogenetic protein-2 were comparable with those of autograft controls and were significantly stronger than those of the placebo (p < 0.05).

Tibial pilon fractures: a comparison of treatment methods.

OBJECTIVE: This retrospective review of surgically treated distal tibia fractures was undertaken to determine whether treatment with open reduction and internal fixation (ORIF) was more efficacious in achieving fracture union than one of two external fixation methods. METHODS: Of the 60 study patients with pilon fractures, 21 patients were treated with an ankle-spanning half-pin external fixator, 15 patients with a single-ring hybrid external fixator, and 24 patients with ORIF. The severity of injuries was similar across groups. RESULTS: There was no significant difference in complication rates between groups, although two below-knee amputations were required in the ORIF group. A greater (p = 0.03) number of malunions occurred in the fractures treated with external fixation when compared with those treated with ORIF. Fractures in the external fixator groups showed this significant tendency to lose their initial adequate reduction, independent of bone grafting or fibula fixation. There was no significant difference between groups in the need for bone grafting. There was a trend for patients treated with a single ring hybrid frame to require late bone grafting for metaphyseal-diaphyseal nonunion. CONCLUSION: External fixation offers advantages in the treatment of the soft-tissue injury associated with pilon fractures, but malunion continues to be a problem with this method of fixation.

Synthesis and preclinical evaluation of glycoconjugate vaccines against group B Streptococcus types VI and VIII.

Group B Streptococcus (GBS) types VI and VIII are prevalent among serotypes isolated from pregnant women in Japan. Maternal vaccination with a safe and effective GBS vaccine has been proposed as a rational approach to prevent neonatal GBS disease. Because antibody specific for the capsular polysaccharide (CPS) antigens of GBS is protective, vaccines were developed with purified type VI and VIII CPS coupled to tetanus toxoid. In rabbits the newly synthesized conjugate vaccines elicited high-titered, type-specific antibody that was opsonically active in vitro. Moreover, litters born to mice actively vaccinated with the conjugate vaccines, in contrast to uncoupled CPS or saline, were protected against an ordinarily lethal challenge of GBS of homologous serotype. GBS types VI and VIII conjugate vaccines of the design presented may be important components of a multivalent GBS vaccine for use in regions where these serotypes predominate.

A comprehensive prognostic index to predict survival based on multiple comorbidities: a focus on breast cancer.

BACKGROUND: The presence of comorbidities often influences clinical decision-making, although many studies exclude patients with comorbid disease for the sake of analysis. OBJECTIVES: The purpose of this study was to develop a Comprehensive Prognostic Index (CPI), designed specifically for breast cancer patients. RESEARCH DESIGN: This study linked Medicare claims with the Kentucky Cancer Registry and developed two models based on 1 year survival; one focused on deaths caused by breast cancer and the other on deaths from all causes. Comorbidities were derived from inpatient and ambulatory claims for up to 2 years before the diagnosis of breast cancer. SUBJECTS: Subjects included a cohort of 848 elderly women first diagnosed with breast cancer in the state of Kentucky in 1993. MEASURES: Each model identified the comorbidities specific to breast cancer that were detrimental to survival, and generated a refined comorbidity index. The CPI integrated these measures with age and stage of cancer into a comprehensive prognostic index. RESULTS: Nearly two-thirds of the patients had evidence of at least one comorbidity. Survival rates decreased with age, more advanced stage, and increased comorbidity burden, as expected. The interaction of comorbidity burden with either age or stage was particularly strong for the older and more advanced stage of cancer. CONCLUSIONS: The CPI could be a useful tool in breast cancer intervention studies and a prognostic aid for clinicians.

Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre.

Selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, in order to improve the prognosis of the normal fetuses. The term elective reduction is used to describe reduction in twin pregnancies for maternal medical conditions, psychological, or socioeconomic reasons. The purpose of this study was to evaluate the factors that influence outcome in such pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59) or elective reduction (n = 23) over a 10-year period. Early procedures, performed < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to-loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of 7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks. In conclusion, outcomes were more favourable among patients who underwent a first trimester procedure. The slight increase in pregnancy loss may be attributed to a higher than expected rate of spontaneous abortions in the first trimester, as manifested by the higher procedure-to-loss interval after a first trimester procedure. These facts underscore the importance of early detection of fetal abnormalities in twin pregnancies by ultrasonography and chorionic villus sampling.