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1.
J Anim Ecol ; 89(6): 1511-1519, 2020 06.
Article in English | MEDLINE | ID: mdl-32145069

ABSTRACT

While the functional response of predators is commonly measured, recent work has revealed that the age and sex composition of prey killed is often a better predictor of prey population dynamics because the reproductive value of adult females is usually higher than that of males or juveniles. Climate is often an important mediating factor in determining the composition of predator kills, but we currently lack a mechanistic understanding of how the multiple facets of climate interact with prey abundance and demography to influence the composition of predator kills. Over 20 winters, we monitored 17 wolf packs in Yellowstone National Park and recorded the sex, age and nutritional condition of kills of their dominant prey-elk-in both early and late winter periods when elk are in relatively good and relatively poor condition, respectively. Nutritional condition (as indicated by per cent marrow fat) of wolf-killed elk varied markedly with summer plant productivity, snow water equivalent (SWE) and winter period. Moreover, marrow was poorer for wolf-killed bulls and especially for calves than it was for cows. Wolf prey composition was influenced by a complex set of climatic and endogenous variables. In early winter, poor plant growth in either year t or t - 1, or relatively low elk abundance, increased the odds of wolves killing bulls relative to cows. Calves were most likely to get killed when elk abundance was high and when the forage productivity they experienced in utero was poor. In late winter, low SWE and a relatively large elk population increased the odds of wolves killing calves relative to cows, whereas low SWE and poor vegetation productivity 1 year prior together increased the likelihood of wolves killing a bull instead of a cow. Since climate has a strong influence on whether wolves prey on cows (who, depending on their age, are the key reproductive components of the population) or lower reproductive value of calves and bulls, our results suggest that climate can drive wolf predation to be more or less additive from year to year.


Subject(s)
Deer , Wolves , Animals , Cattle , Female , Male , Parks, Recreational , Population Dynamics , Predatory Behavior
2.
Obes Surg ; 30(4): 1506-1514, 2020 04.
Article in English | MEDLINE | ID: mdl-32043255

ABSTRACT

INTRODUCTION: Single-anastomosis duodenal switch has been suggested to be an effective bariatric procedure that offers excellent weight loss and by lengthening the common channel the potential to reduce micronutrient deficiencies. PURPOSE: To evaluate the weight loss, comorbidity resolution and the 1-year nutritional outcomes of the single-anastomosis duodenal switch (SADS) procedure. SETTING: Multiple US Hospitals. METHODS: From October 2014 to January 2017, 120 patients were enrolled at six sites across the USA and underwent the SADS procedure. Weight loss, comorbidities, quality of life, and adverse events were followed post-procedure for 12 months. RESULTS: At 1, 6, and 12 months, 98.3%, 85.5%, and 77.1% of the patients were available for assessment, respectively. At 12 months, patients showed significantly reduced body mass index when compared to baseline (46.8 ± 5.8 vs 29.8 ± 4.4, P < 0.001 respectively). Sixty-five patients had type 2 diabetes at baseline; however, 11 patients lost to follow-up. Of the available data (54 patients), 96.3% of the patients had a resolution of type 2 diabetes by 12 months with a mean A1C reduction from 7.8 ± 1.6 to 5.3 ± 0.7. Additionally, there were reductions in hyperlipidemia, sleep apnea, and hypertension at 12 months. Patient gastroesophageal reflux disease satisfaction and quality of life (SF-36) scores were significantly higher at 12 months post-procedure (P < 0.001 in all cases) while 12-month protein levels remained at normal values. There were abnormalities of parathyroid hormone and vitamin D at 1 year with all other nutritional markers being not significantly different at 1 year from baseline. There were 10, IIIb, or greater complications according to the Clavien-Dindo scoring system during the study period, not all of which were related to the surgery. CONCLUSIONS: SADS is a highly efficacious weight loss procedure with significant comorbidity reduction at 1 year. At 1 year, complications and vitamin and mineral deficits appear to be consistent with other malabsorption operations. Long-term follow-up is needed, especially around complications and vitamin deficiencies.


Subject(s)
Diabetes Mellitus, Type 2 , Gastric Bypass , Obesity, Morbid , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/surgery , Duodenum/surgery , Humans , Obesity, Morbid/surgery , Quality of Life
3.
J Anim Ecol ; 89(1): 120-131, 2020 01.
Article in English | MEDLINE | ID: mdl-30838656

ABSTRACT

The extent to which prey space use actively minimizes predation risk continues to ignite controversy. Methodological reasons that have hindered consensus include inconsistent measurements of predation risk, biased spatiotemporal scales at which responses are measured and lack of robust null expectations. We addressed all three challenges in a comprehensive analysis of the spatiotemporal responses of adult female elk (Cervus elaphus) to the risk of predation by wolves (Canis lupus) during winter in northern Yellowstone, USA. We quantified spatial overlap between the winter home ranges of GPS-collared elk and three measures of predation risk: the intensity of wolf space use, the distribution of wolf-killed elk and vegetation openness. We also assessed whether elk varied their use of areas characterized by more or less predation risk across hours of the day, and estimated encounter rates between simultaneous elk and wolf pack trajectories. We determined whether observed values were significantly lower than expected if elk movements were random with reference to predation risk using a null model approach. Although a small proportion of elk did show a tendency to minimize use of open vegetation at specific times of the day, overall we highlight a notable absence of spatiotemporal response by female elk to the risk of predation posed by wolves in northern Yellowstone. Our results suggest that predator-prey interactions may not always result in strong spatiotemporal patterns of avoidance.


Subject(s)
Deer , Wolves , Animals , Female , Movement , Predatory Behavior , Seasons
4.
Ecol Lett ; 22(11): 1724-1733, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31373137

ABSTRACT

Many ecosystems contain sympatric predator species that hunt in different places and times. We tested whether this provides vacant hunting domains, places and times where and when predators are least active, that prey use to minimize threats from multiple predators simultaneously. We measured how northern Yellowstone elk (Cervus elaphus) responded to wolves (Canis lupus) and cougars (Puma concolor), and found that elk selected for areas outside the high-risk domains of both predators consistent with the vacant domain hypothesis. This enabled elk to avoid one predator without necessarily increasing its exposure to the other. Our results demonstrate how the diel cycle can serve as a key axis of the predator hunting domain that prey exploit to manage predation risk from multiple sources. We argue that a multi-predator, spatiotemporal framework is vital to understand the causes and consequences of prey spatial response to predation risk in environments with more than one predator.


Subject(s)
Deer , Wolves , Animals , Ecosystem , Predatory Behavior
5.
Ecol Evol ; 8(22): 11158-11168, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30519433

ABSTRACT

Top predators have cascading effects throughout the food web, but their impacts on scavenger abundance are largely unknown. Gray wolves (Canis lupus) provide carrion to a suite of scavenger species, including the common raven (Corvus corax). Ravens are wide-ranging and intelligent omnivores that commonly take advantage of anthropogenic food resources. In areas where they overlap with wolves, however, ravens are numerous and ubiquitous scavengers of wolf-acquired carrion. We aimed to determine whether subsidies provided through wolves are a limiting factor for raven populations in general and how the wolf reintroduction to Yellowstone National Park in 1995-1997 affected raven population abundance and distribution on the Yellowstone's Northern Range specifically. We counted ravens throughout Yellowstone's Northern Range in March from 2009 to 2017 in both human-use areas and wolf habitat. We then used statistics related to the local wolf population and the winter weather conditions to model raven abundance during our study period and predict raven abundance on the Northern Range both before and after the wolf reintroduction. In relatively severe winters with greater snowpack, raven abundance increased in areas of human use and decreased in wolf habitat. When wolves were able to acquire more carrion, however, ravens increased in wolf habitat and decreased in areas with anthropogenic resources. Raven populations prior to the wolf reintroduction were likely more variable and heavily dependent on ungulate winter-kill and hunter-provided carcasses. The wolf recovery in Yellowstone helped stabilize raven populations by providing a regular food supply, regardless of winter severity. This stabilization has important implications for effective land management as wolves recolonize the west and global climate patterns change.

6.
Nat Ecol Evol ; 2(10): 1619-1625, 2018 10.
Article in English | MEDLINE | ID: mdl-30177803

ABSTRACT

Sexually selected weapons evolved to maximize the individual reproductive success of males in many polygynous breeding species. Many weapons are also retained outside of reproductive periods for secondary reasons, but the importance of these secondary functions is poorly understood. Here we leveraged a unique opportunity from the predator-prey system in northern Yellowstone National Park, WY, USA to evaluate whether predation by a widespread, coursing predator (wolves) has influenced a specific weapon trait (antler retention time) in their primary cervid prey (elk). Male elk face a trade-off: individuals casting antlers early begin regrowth before other males, resulting in relatively larger antlers the following year, and thus greater reproductive success, as indicated by research with red deer. We show, however, that male elk that cast their antlers early are preferentially hunted and killed by wolves, despite early casters being in better nutritional condition than antlered individuals. Our results run counter to classic expectations of coursing predators preferring poorer-conditioned individuals, and in so doing, reveal an important secondary function for an exaggerated sexually selected weapon-predatory deterrence. We suggest this secondary function played a key evolutionary role in elk; uniquely among North American cervids, they retain their antlers long after they fulfil their primary role in reproduction.


Subject(s)
Antlers/physiology , Deer/physiology , Food Chain , Predatory Behavior , Wolves/physiology , Animals , Antlers/growth & development , Deer/growth & development , Female , Male , Parks, Recreational , Wyoming
7.
Proc Biol Sci ; 284(1848)2017 02 08.
Article in English | MEDLINE | ID: mdl-28179516

ABSTRACT

Trophic interactions are a fundamental topic in ecology, but we know little about how competition between apex predators affects predation, the mechanism driving top-down forcing in ecosystems. We used long-term datasets from Scandinavia (Europe) and Yellowstone National Park (North America) to evaluate how grey wolf (Canis lupus) kill rate was affected by a sympatric apex predator, the brown bear (Ursus arctos). We used kill interval (i.e. the number of days between consecutive ungulate kills) as a proxy of kill rate. Although brown bears can monopolize wolf kills, we found no support in either study system for the common assumption that they cause wolves to kill more often. On the contrary, our results showed the opposite effect. In Scandinavia, wolf packs sympatric with brown bears killed less often than allopatric packs during both spring (after bear den emergence) and summer. Similarly, the presence of bears at wolf-killed ungulates was associated with wolves killing less often during summer in Yellowstone. The consistency in results between the two systems suggests that brown bear presence actually reduces wolf kill rate. Our results suggest that the influence of predation on lower trophic levels may depend on the composition of predator communities.


Subject(s)
Competitive Behavior , Predatory Behavior , Ursidae , Wolves , Animals , Deer , Food Chain , North America , Scandinavian and Nordic Countries
8.
Bioorg Med Chem ; 24(24): 6429-6439, 2016 12 15.
Article in English | MEDLINE | ID: mdl-27614915

ABSTRACT

The efficacy of plazomicin for pneumonic plague was evaluated in a non-human primate model. African Green monkeys challenged with a lethal aerosol of Yersinia pestis [median (range) of 98 (15-331) LD50s] received placebo (n=12) or 'humanized' dose regimens (6.25, 12.5 or 25mg/kg every 24h) of plazomicin (n=52) after the onset of fever for a duration of 5 or 10days. All animals treated with placebo died, while 36 plazomicin-treated animals survived through study end. The majority (33/36) were either in the 10-day (high-/mid-/low-dose) or 5-day high-dose groups. The findings suggest an exposure range of plazomicin for treatment of pneumonic/bacteremic Y. pestis infection in humans.


Subject(s)
Disease Models, Animal , Plague/drug therapy , Sisomicin/analogs & derivatives , Animals , Chlorocebus aethiops , Dose-Response Relationship, Drug , Molecular Conformation , Sisomicin/chemistry , Sisomicin/therapeutic use
10.
Antimicrob Agents Chemother ; 58(8): 4253-6, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24867992

ABSTRACT

The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics.


Subject(s)
Animal Husbandry/legislation & jurisprudence , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Microbial , United States Government Agencies/legislation & jurisprudence , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/economics , Clinical Trials as Topic , Humans , Information Dissemination/ethics , Private Sector/legislation & jurisprudence , Quality Control , United States
11.
J Anim Ecol ; 81(3): 553-63, 2012 May.
Article in English | MEDLINE | ID: mdl-22260633

ABSTRACT

1. For large predators living in seasonal environments, patterns of predation are likely to vary among seasons because of related changes in prey vulnerability. Variation in prey vulnerability underlies the influence of predators on prey populations and the response of predators to seasonal variation in rates of biomass acquisition. Despite its importance, seasonal variation in predation is poorly understood. 2. We assessed seasonal variation in prey composition and kill rate for wolves Canis lupus living on the Northern Range (NR) of Yellowstone National Park. Our assessment was based on data collected over 14 winters (1995-2009) and five spring-summers between 2004 and 2009. 3. The species composition of wolf-killed prey and the age and sex composition of wolf-killed elk Cervus elaphus (the primary prey for NR wolves) varied among seasons. 4. One's understanding of predation depends critically on the metric used to quantify kill rate. For example, kill rate was greatest in summer when quantified as the number of ungulates acquired per wolf per day, and least during summer when kill rate was quantified as the biomass acquired per wolf per day. This finding contradicts previous research that suggests that rates of biomass acquisition for large terrestrial carnivores tend not to vary among seasons. 5. Kill rates were not well correlated among seasons. For example, knowing that early-winter kill rate is higher than average (compared with other early winters) provides little basis for anticipating whether kill rates a few months later during late winter will be higher or lower than average (compared with other late winters). This observation indicates how observing, for example, higher-than-average kill rates throughout any particular season is an unreliable basis for inferring that the year-round average kill rate would be higher than average. 6. Our work shows how a large carnivore living in a seasonal environment displays marked seasonal variation in predation because of changes in prey vulnerability. Patterns of wolf predation were influenced by the nutritional condition of adult elk and the availability of smaller prey (i.e. elk calves, deer). We discuss how these patterns affect our overall understanding of predator and prey population dynamics.


Subject(s)
Predatory Behavior/physiology , Seasons , Wolves/physiology , Aging , Animals , Artiodactyla , Female , Male , Time Factors
12.
Biosecur Bioterror ; 9(4): 351-60, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22053938

ABSTRACT

In recent years, there has been an increase in the perceived threat of biological agents being used against civilian populations. This has prompted an urgent need for the development and procurement of medical countermeasures (MCMs) against highly pathogenic viruses that can prevent morbidity and mortality from infections caused by these agents. To date, antiviral drug development has been largely focused on clinically prevalent chronic infections due to their commercial viability. This has left a huge gap in the drug development path for acute infections of biodefense importance. In this review, we discuss the antiviral research and development initiatives focusing specifically on poxviruses, filoviruses, and equine encephalitis viruses (EEV). We discuss the benefits and technical challenges in the current development strategies and the hurdles in the licensure path for MCMs against these highly pathogenic viruses under the FDA Animal Rule, and we provide recommendations for the path forward.


Subject(s)
Antiviral Agents/therapeutic use , Bioterrorism , Disaster Planning/organization & administration , Immunotherapy/methods , Virus Diseases/prevention & control , Animals , Humans , Virus Diseases/transmission
13.
PLoS One ; 6(3): e17332, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-21390256

ABSTRACT

BACKGROUND: Understanding how kill rates vary among seasons is required to understand predation by vertebrate species living in temperate climates. Unfortunately, kill rates are only rarely estimated during summer. METHODOLOGY/PRINCIPAL FINDINGS: For several wolf packs in Yellowstone National Park, we used pairs of collared wolves living in the same pack and the double-count method to estimate the probability of attendance (PA) for an individual wolf at a carcass. PA quantifies an important aspect of social foraging behavior (i.e., the cohesiveness of foraging). We used PA to estimate summer kill rates for packs containing GPS-collared wolves between 2004 and 2009. Estimated rates of daily prey acquisition (edible biomass per wolf) decreased from 8.4±0.9 kg (mean ± SE) in May to 4.1±0.4 kg in July. Failure to account for PA would have resulted in underestimating kill rate by 32%. PA was 0.72±0.05 for large ungulate prey and 0.46±0.04 for small ungulate prey. To assess seasonal differences in social foraging behavior, we also evaluated PA during winter for VHF-collared wolves between 1997 and 2009. During winter, PA was 0.95±0.01. PA was not influenced by prey size but was influenced by wolf age and pack size. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that seasonal patterns in the foraging behavior of social carnivores have important implications for understanding their social behavior and estimating kill rates. Synthesizing our findings with previous insights suggests that there is important seasonal variation in how and why social carnivores live in groups. Our findings are also important for applications of GPS collars to estimate kill rates. Specifically, because the factors affecting the PA of social carnivores likely differ between seasons, kill rates estimated through GPS collars should account for seasonal differences in social foraging behavior.


Subject(s)
Predatory Behavior/physiology , Seasons , Social Behavior , Wolves/physiology , Animals , Computer Simulation , Geographic Information Systems , Geography , United States
14.
Science ; 319(5868): 1335, 2008 Mar 07.
Article in English | MEDLINE | ID: mdl-18323431
15.
J Am Chem Soc ; 127(42): 14756-68, 2005 Oct 26.
Article in English | MEDLINE | ID: mdl-16231930

ABSTRACT

This contribution describes the implementation of the binuclear organotitanium "constrained geometry catalysts" (CGCs), (mu-CH(2)CH(2)-3,3'){(eta(5)-indenyl)[1-Me(2)Si((t)()BuN)](TiMe(2))}(2)[EBICGC(TiMe(2))(2); Ti(2)] and (mu-CH(2)-3,3'){(eta(5)-indenyl)[1-Me(2)Si((t)BuN)](TiMe(2))}(2)[MBICGC(TiMe(2))(2); C1-Ti(2)], in combination with the bifunctional bisborane activator 1,4-(C(6)F(5))(2)BC(6)F(4)B(C(6)F(5))(2) (BN(2)) in ethylene + olefin copolymerization processes. Specifically examined are the classically poorly responsive 1,1-disubstituted comonomers, methylenecyclopentane (C), methylenecyclohexane (D), 1,1,2-trisubstituted 2-methyl-2-butene (E), and isobutene (F). For the first three comonomers, this represents the first report of their incorporation into a polyethylene backbone via a coordination polymerization process. C and D are incorporated via a ring-unopened pathway, and E is incorporated via a novel pathway involving 2-methyl-1-butene enchainment in the copolymer backbone. In ethylene copolymerization, Ti(2) + BN(2) enchains approximately 2.5 times more C, approximately 2.5 times more D, and approximately 2.3 times more E than the mononuclear catalyst analogue [1-Me(2)Si(3-ethylindenyl)((t)BuN)]TiMe(2) (Ti(1)) + B(C(6)F(5))(3) (BN) under identical polymerization conditions. Polar solvents are found to weaken the catalyst-cocatalyst ion pairing, thus influencing the comonomer enchainment selectivity.


Subject(s)
Alkenes/chemical synthesis , Ethylenes/chemistry , Metals, Heavy/chemistry , Organometallic Compounds/chemistry , Alkenes/chemistry , Carbon Isotopes , Catalysis , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis
16.
Plant J ; 41(6): 801-14, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15743446

ABSTRACT

Nicotiana benthamiana leaves display a visible plant cell death response when infiltrated with a high titer inoculum of the non-host pathogen, Xanthomonas campestris pv. vesicatoria (Xcv). This visual phenotype was used to identify overlapping cosmid clones from a genomic cosmid library constructed from the Xcv strain, GM98-38. Individual cosmid clones from the Xcv library were conjugated into X. campestris pv. campestris (Xcc) and exconjugants were scored for an altered visual high titer inoculation response in N. benthamiana. The molecular characterization of the cosmid clones revealed that they contained a novel gene, xopX, that encodes a 74-kDa type III secretion system (TTSS) effector protein. Agrobacterium-mediated transient expression of XopX in N. benthamiana did not elicit the plant cell death response although detectable XopX protein was produced. Interestingly, the plant cell death response occurred when the xopX Agrobacterium-mediated transient expression construct was co-inoculated with strains of either XcvDeltaxopX or Xcc, both lacking xopX. The co-inoculation complementation of the plant cell death response also depends on whether the Xanthomonas strains contain an active TTSS. Transgenic 35S-xopX-expressing N. benthamiana plants also have the visible plant cell death response when inoculated with the non-xopX-expressing strains XcvDeltaxopX and Xcc. Unexpectedly, transgenic 35S-xopX N. benthamiana plants displayed enhanced susceptibility to bacterial growth of Xcc as well as other non-xopX-expressing Xanthomonas and Pseudomonas strains. This result is also consistent with the increase in bacterial growth on wild type N. benthamiana plants observed for Xcc when XopX is expressed in trans. Furthermore, XopX contributes to the virulence of Xcv on host pepper (Capsicum annuum) and tomato (Lycopersicum esculentum) plants. We propose that the XopX bacterial effector protein targets basic innate immunity in plants, resulting in enhanced plant disease susceptibility.


Subject(s)
Bacterial Proteins/physiology , Nicotiana/microbiology , Plant Diseases/microbiology , Xanthomonas campestris/physiology , Amino Acid Sequence , Base Sequence , Biological Transport, Active , Cell Death , Conserved Sequence , Membrane Transport Proteins , Molecular Sequence Data , Plant Leaves/microbiology , Virulence , Xanthomonas campestris/pathogenicity
18.
South Med J ; 97(8): 715-9, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15352662

ABSTRACT

OBJECTIVE: Tree stand falls are a well-known cause of hunting-related injury. Spine and brain injuries associated with these falls result in a significant incidence of permanent disability. Prior studies indicate that hunting tree stand injuries are largely preventable with the proper use of safety belts; however, compliance with safety belt use is variable. The purposes of this study were to determine 1) current compliance with safety belt use, 2) alterations in the spectrum of injury, and 3) causes of the falls. METHODS: From January 1996 to October 2001, 51 tree stand-related injuries referred to either of two regional trauma centers or their region's medical examiner's office were reviewed. Data had been recorded in each hospital's trauma registry, and the registries were searched for falls. Medical records were reviewed for additional data retrospectively, with an emphasis on determining the use of safety belts, and mechanisms contributing to the fall. RESULTS: Fifty-one cases of tree stand-associated injuries were identified. These injuries all occurred in men, with a mean age of 42.6 years (range, 22-69 years). Alcohol use was present in 10% of patients and in two of the three deaths. The mean Injury Severity Score was 18.1 (range, 2-75). The most common injuries were spinal fractures (51% of series) and extremity fractures (41% of series). Closed head injuries were identified in 24% and lung injuries were identified in 22% of patients. Abdominal visceral injuries were present in 8% and genitourinary injuries were present in 4%. Three patients died. In addition to injury from the fall, a significant number (six patients [12%]) had additional morbidity from exposure. Only two patients reported the use of a safety belt (4% of series). There were no cases of gunshot wounds in this review, either self-inflicted or hunter-related. The chief reasons reported for these falls were errors in placement that resulted in structural failure of the stand, or errors made while climbing into or out of the stand (50% of falls). CONCLUSION: Devastating spine and brain injuries continue to occur after falls from tree stands during recreational hunting when safety belts are not used. Our results suggest a continuing need for the education of hunters concerning safe tree stand hunting practices, including proper methods of stand placement, assessment of tree branch strength, avoidance of fatigue and alcohol, anticipation of firearm recoil, and proper methods of stand entrance and exit. Trauma prevention programs directed toward heightened public awareness of these injuries during hunting season are still needed.


Subject(s)
Accidental Falls/statistics & numerical data , Athletic Injuries/epidemiology , Athletic Injuries/etiology , Leisure Activities , Adult , Aged , Humans , Male , Maryland/epidemiology , Middle Aged , New York/epidemiology , Trees
19.
J Am Chem Soc ; 125(48): 14768-83, 2003 Dec 03.
Article in English | MEDLINE | ID: mdl-14640652

ABSTRACT

C(2)-symmetric bis(oxazolinato)lanthanide complexes of the type [(4R,5S)-Ph(2)Box]La[N(TMS)(2)](2), [(4S,5R)-Ar(2)Box]La[N(TMS)(2)](2), and [(4S)-Ph-5,5-Me(2)Box]La[N(TMS)(2)](2) (Box = 2,2'-bis(2-oxazoline)methylenyl; Ar = 4-tert-butylphenyl, 1-naphthyl; TMS = SiMe(3)) serve as precatalysts for the efficient enantioselective intramolecular hydroamination/cyclization of aminoalkenes and aminodienes. These new catalyst systems are conveniently generated in situ from the known metal precursors Ln[N(TMS)(2)](3) or Ln[CH(TMS)(2)](3) (Ln = La, Nd, Sm, Y, Lu) and 1.2 equiv of commercially available or readily prepared bis(oxazoline) ligands such as (4R,5S)-Ph(2)BoxH, (4S,5R)-Ar(2)BoxH, and (4S)-Ph-5,5-Me(2)BoxH. The X-ray crystal structure of [(4S)-(t)BuBox]Lu[CH(TMS)(2)](2) provides insight into the structure of the in situ generated precatalyst species. Lanthanides having the largest ionic radii exhibit the highest turnover frequencies as well as enantioselectivities. Reaction rates maximize near 1:1 BoxH:Ln ratio (ligand acceleration); however, increasing the ratio to 2:1 BoxH:Ln decreases the reaction rate, while affording enantiomeric excesses similar to the 1:1 BoxH:Ln case. A screening study of bis(oxazoline) ligands reveals that aryl stereodirecting groups at the oxazoline ring 4 position and additional substitution (geminal dimethyl or aryl) at the 5 position are crucial for high turnover frequencies and good enantioselectivities. The optimized precatalyst, in situ generated [(4R,5S)-Ph(2)Box]La[N(TMS)(2)](2), exhibits good rates and enantioselectivities, comparable to or greater than those achieved with chiral C(1)-symmetric organolanthanocene catalysts, even for poorly responsive substrates (up to 67% ee at 23 degrees C). Kinetic studies reveal that hydroamination rates are zero order in [amine substrate] and first order in [catalyst], implicating the same general mechanism for organolanthanide-catalyzed hydroamination/cyclizations (intramolecular turnover-limiting olefin insertion followed by the rapid protonolysis of an Ln-C bond by amine substrate) and implying that the active catalytic species is monomeric.

20.
J Vasc Surg ; 38(6): 1154-61, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14681599

ABSTRACT

PURPOSE: A few nonrandomized studies have reported the natural history of carotid artery stenosis (CAS) contralateral to carotid endarterectomy (CEA). This study analyzed this condition with data from two randomized prospective trials. METHODS: The contralateral carotid arteries in 534 patients from two randomized trials that compared CEA with primary closure versus patching were followed up clinically and with duplex ultrasound scanning at 1 month and then every 6 months. CAS was classified as less than 50%, 50% to 79%, 80% to 99%, and occlusion. Late contralateral CEA was performed to treat significant CAS. Progression was defined as progress to a higher category of stenosis. Kaplan-Meier life table analysis was used to estimate freedom from progression of CAS. The correlation of risk factors and CAS progression was also analyzed. RESULTS: Of 534 patients, 61 had initial contralateral CEA and 53 had contralateral occlusion. Overall, CAS progressed in 109 of 420 patients (26%) at mean follow-up of 41 months. Progression of CAS was noted in 5 of 162 patients (3%) with baseline normal carotid arteries. CAS progressed in 56 of 157 patients (36%) with less than 50% stenosis versus 45 of 95 patients (47%) with 50% to 79% stenosis (P =.003). Median time to progression was 24 months for less than 50% CAS, and 12 months for 50% to 79% CAS (P =.035). At 1, 2, 3, 4, and 5 years, freedom from disease progression in patients with baseline CAS <50% was 95%, 78%, 69%, 61%, 48%, respectively, and in patients with 50% to 79% CAS was 75%, 61%, 51%, 43%, and 33%, respectively (P =.003). Freedom from progression in patients with baseline normal carotid arteries at 1 through 5 years was 99%, 98%, 96%, 96%, and 94%, respectively. Late neurologic events referable to the CCA were infrequent (28 of 420 [6.7%] in the entire series; 28 of 258 [10.9%] patients with contralateral CAS), and included 10 strokes (2.4%) and 18 transient ischemic attacks (4.3%). However, late contralateral CEA was performed in 62 patients (62 of 420 [15%] in the entire series; 62 of 258 [24%] patients with contralateral CAS). Survival rates were 96%, 92%, 90%, 87%, and 82%, respectively, at 1 through 5 years. CONCLUSIONS: Progression of CCA stenosis was noted in a significant number of patients with baseline contralateral CAS. Serial clinical studies and duplex ultrasound scanning every 6 to 12 months in patients with 50% to 79% CAS, and every 12 to 24 months in patients with 50% or less CAS is adequate.


Subject(s)
Carotid Stenosis/physiopathology , Carotid Stenosis/surgery , Collateral Circulation/physiology , Endarterectomy, Carotid , Adult , Aged , Aged, 80 and over , Carotid Stenosis/complications , Female , Follow-Up Studies , Humans , Ischemic Attack, Transient/etiology , Ischemic Attack, Transient/mortality , Ischemic Attack, Transient/physiopathology , Life Tables , Male , Middle Aged , Prospective Studies , Randomized Controlled Trials as Topic , Severity of Illness Index , Stroke/etiology , Stroke/mortality , Stroke/physiopathology , Time Factors , Treatment Outcome
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