Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
J Chiropr Educ ; 38(1): 38-41, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38323347

RESUMO

OBJECTIVE: The doctor of chiropractic program (DCP) graduate must demonstrate competency in clinical research literacy (CRL), per accreditation standards. This study aimed to compare student CRL knowledge, confidence, and attitudes between the beginning and end of their DCP. METHODS: We collected data on 245 matriculating students' CRL knowledge, confidence, and attitudes between 2017 and 2018. In 2021 and 2022, 78 of these students enrolled in a course with an extra credit assignment that was used to re-collect CRL data as they approached graduation. We assessed changes between entry and exit using statistical analyses in STATA17. RESULTS: Paired data were collected for 56 students. The mean CRL scores on a scale of 10 at the DCP beginning and end were 5.25 (SD 2.06) and 6.54 (SD 1.89), respectively (p = .0001). We observed statistically significant (p ≤ .05) positive changes in students' abilities to answer questions about Medical Subject Headings, the hierarchy of evidence, systematic reviews, meta-analyses, and the limitations of abstracts. There was also a statistically significant increase in confidence, with over 80% of students nearing graduation reporting good or excellent abilities to find and judge health information for their patients. The proportion of students who envisioned searching a database to help manage a challenging clinical case decreased from 96% to 89% (p > .05). The proportion seeing themselves submitting a case report for publication declined from 16% to 4% (p ≤ .05). CONCLUSION: Students' self-perceived CRL abilities and knowledge improved between the beginning and end of their DCP; however, their attitudes toward applying these in practice declined.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32974313

RESUMO

Due to the severity and frequency of cervical spine injuries, the neck injury criterion (Nij) was developed to provide a quantitative relationship between forces and moments of the upper neck with accompanied injury risk. The present study was undertaken to evaluate differences in calculated Nij for the Global Human Body Model Consortium's detailed and simplified average 50th percentile male models. The simplified model is a computationally light version of the more detailed model and therefore it is of interest to achieve similar Nij values between the two models. These models were compared in 15 match paired conditions of rigid head impact and a mixture of seven full body rigid hub and sled pulses, for 44 total simulations. Collectively, Nij values of the simplified model were found to exhibit a second-degree polynomial fit, allowing for a conversion to the prediction of the detailed model. Correlates were also derived for impact and inertial loading cases individually, for which the latter may be the subject of future work. The differences in Nij may be attributed to a variety of modeling approach differences related to neck muscles (attachment location and morphometric implementation), localization of head mass within the M50-OS, head geometry, and intervertebral joint space properties. With a primary focus on configurations in the anterior-posterior direction, there is a potential limitation in extensibility to lateral loading cases. In response to the relatively low Nij values exhibited, future work should evaluate the appropriateness of the established critical intercepts of Nij for computational human body models.

3.
Traffic Inj Prev ; 20(8): 832-837, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31549531

RESUMO

Objective: The goal of this study was to implement active musculature into the Global Human Body Models Consortium (GHBMC) average male simplified occupant model (M50-OS v2) and validate its performance in low-speed frontal crash scenarios.Methods: Volunteer and postmortem human subjects (PMHS) data from low-speed frontal sled tests by Beeman et al., including 2.5 and 5.0 g acceleration pulses, were used to simulate events in LS-DYNA. All muscles were modeled as 1D beam elements and assigned a Hill-type muscle material. From the output of proportional-integral-derivative (PID) controllers, the activation level for each muscle was calculated using a sigmoid function, representing the firing rate of motor neurons. The PID controller attempts to preserve the initial posture of the model. Percentage muscle contribution for all skeletal muscles was precalculated using the M50-OS with active muscles (M50-OS + Active). The M50-OS + Active employs varying levels of neural delays to represent volunteer relaxed and braced conditions, taken from literature. Braced condition experiments were simulated using elevated joint angle set values for the PID controller. The M50-OS + Active model was used to simulate 2 muscle conditions (relaxed and braced) at 2 pulse severities (2.5 and 5.0 g). A control set of simulations was conducted to compare the effect of adding active muscle. Ten whole-body simulations were conducted.Results: The results from volunteer simulations showed a strong dependence of reaction loads and kinematics on muscle activation. Compared to baseline, M50-OS, at 5.0 g acceleration, 33.3% and 7.6% decreases were observed in the overall head kinematics of the M50-OS + Active for the braced and relaxed conditions, respectively. Regarding the anterior direction, similar reductions in overall kinematics were observed for both volunteer test conditions. In comparison to control simulations in which no active muscle was implemented, objective evaluation scores increased markedly at both speeds for the braced condition. Little to no gain was found in the relaxed condition.Conclusions: The results justify the need for use of an active human body model for predicting low-speed frontal kinematics, particularly in the braced condition. Head kinematics were reduced when using active modeling for all simulations (braced and relaxed).


Assuntos
Acidentes de Trânsito , Automóveis , Cabeça/fisiologia , Músculo Esquelético/fisiologia , Aceleração , Fenômenos Biomecânicos , Cadáver , Corpo Humano , Humanos , Masculino , Modelos Teóricos , Neurônios Motores , Postura , Ferimentos e Lesões/prevenção & controle
4.
Case Rep Surg ; 2019: 2831234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428507

RESUMO

BACKGROUND: Duodenal diverticula tend to be asymptomatic; however, patients may develop duodenal diverticulitis. CASE PRESENTATION: A 66-year-old Caucasian man presented to our emergency room with a two-day history of right-sided abdominal pain, chills, tachycardia, nausea, and emesis. His WBC, lactic acid, and bilirubin were elevated. CT-scan revealed an inflammatory process involving the gallbladder, the duodenum and ascending colon, a mesenteric soft tissue mass, and a diverticulum of the second portion of the duodenum. He was admitted, antibiotics were started, and he improved clinically over the next 36 hours. Repeat triple contrast CT-scan showed a two cm pseudoaneurysm (PA) of the pancreaticoduodenal artery causing a mesenteric hematoma. The inflammatory changes had significantly improved, and WBC and CRP were normalizing. Repeat CT-scan three days later demonstrated an interval increase in size of the PA. Angiography through celiac access and gastroduodenal artery demonstrated predominant inflow to the PA from the inferior pancreaticoduodenal artery. The superior mesenteric artery was accessed showing a replaced right hepatic artery hindering access to the branch feeding the PA. The patient was transferred to a specialized facility where ultimately occlusion of the PA inflow was obtained. The patient recovered without any complication from this rare condition. CONCLUSION: This seems to be the first reported case of duodenal diverticulitis causing a PA of the pancreaticoduodenal artery. Antibiotic therapy together with percutaneous embolization of the bleeding source resulted in a good outcome.

5.
Case Rep Surg ; 2019: 1072821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183241

RESUMO

BACKGROUND: Lumbar hernias are rare abdominal hernias. Surgery is the only treatment option but remains challenging. Posterior incisional hernias are even rarer especially with incarceration of intra-abdominal contents. CASE PRESENTATION: A 68-year old female presented with a 3-day history of worsening acute abdominal pain and distension, with multiple episodes of emesis. A CT scan indicated a large incarcerated posterolateral abdominal hernia. The patient had a history of resection of a sarcoma on her back as a child and also received chemotherapy and radiation. During emergency laparoscopy, a hemorrhagic small bowel segment incarcerated in the hernia was reduced and resected, and the distended small bowel was decompressed. An elective hernia repair was scheduled. After temporary clinical improvement, the patient again developed abdominal pain, distention, and emesis. During emergency laparotomy, a large hematoma in the right flank was found and partially evacuated. The right colon was mobilized out of the hernia and the duodenum was kocherized. A 20 × 20 cm BIO-A mesh was placed on top of the Gerota fascia and cranially tucked under liver segment VI. Anteriorly, the mesh was fixated with absorbable tacks. The duodenum and colon were placed into the mesh pocket. A postoperative CT scan identified a 2 cm pseudoaneurysm of a side branch of a lumbar artery, and the bleeding source was embolized. The postoperative course was complicated by Clostridium difficile-associated colitis, but ultimately, the patient recovered fully. At 6-month follow-up, there was no evidence for a recurrent hernia. DISCUSSION: There is a paucity of literature concerning lumbar incisional hernias. Repair with bioabsorbable mesh seems feasible, but longer follow-up is necessary as the mesh was placed in an unusual fashion due to the retroperitoneal hematoma. The exact cause of the hemorrhage is unclear and may have been caused during the initial incarceration, during surgery, or may be a late complication of her previous radiation.

6.
J Acoust Soc Am ; 145(4): EL272, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31046329

RESUMO

An investigation into the perceptual threshold of apparent source width (ASW) in relation to a single reflection azimuth was performed in binaural reproduction. In the presence of a direct sound, subjects compared the ASW produced by a single 90° reference reflection against ASW produced by a test reflection with a varying angle for four reflection delay times between 5 and 30 ms. Threshold angles were found to be approximately 40° and 130°, and did not appear to be dependent on delay time. It was also found that these threshold angles were associated to saturation in [1-IACCE3] versus reflection azimuth.

7.
Int J Mol Sci ; 19(11)2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30469350

RESUMO

Biotherapeutics are a rapidly growing portion of the total pharmaceutical market accounting for almost one-half of recent new drug approvals. A major portion of these approvals each year are monoclonal antibodies (mAbs). During development, non-clinical pharmacology and toxicology testing of mAbs differs from that done with chemical entities since these biotherapeutics are derived from a biological source and therefore the animal models must share the same epitopes (targets) as humans to elicit a pharmacological response. Mechanisms of toxicity of mAbs are both pharmacological and non-pharmacological in nature; however, standard in silico predictive toxicological methods used in research and development of chemical entities currently do not apply to these biotherapeutics. Challenges and potential opportunities exist for new methodologies to provide a more predictive program to assess and monitor potential adverse drug reactions of mAbs for specific patients before and during clinical trials and after market approval.


Assuntos
Anticorpos Monoclonais/toxicidade , Terapia Biológica/métodos , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 1763-1766, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30440736

RESUMO

As the duration of manned missions outside of the Earth's protective shielding increase, astronauts are at risk for exposure to space radiation. Various organ systems may be damaged due to exposure. This study investigates the bone strength changes using finite element modeling of Long Evans rats (n=85) subjected to graded, head-only proton (0, 10, 25, and 100 cGy, 150 MeV/n) and 28silicon (0, 10, 25, and 50 cGy, 300 MeV/n) radiation. The strength of the femoral neck will be examined due its clinical relevance to hip fractures. It has been shown in previous studies that bone mineral density was not reduced at the site of fracture. These findings question whether measurements of bone mineral density may be used to assess risk of hip fracture. The mechanisms leading to the irregular relationship between bone density and strength are still uncertain within literature and investigated to greater extent in clinical applications. Finite element analysis within this study simulated physiological loading of the femoral neck. No significant changes in femoral neck strength were found across doses of proton or 28silicon head-only radiation. Future work includes performing mechanical testing of the bone samples. Moving from mouse to larger animal models may also provide the increased lifespan for assessing the long-term outcomes of radiation exposure.


Assuntos
Radiação de Fundo , Densidade Óssea , Colo do Fêmur , Análise de Elementos Finitos , Modelos Biológicos , Animais , Densidade Óssea/efeitos da radiação , Colo do Fêmur/efeitos da radiação , Fraturas do Quadril , Camundongos , Ratos , Ratos Long-Evans
9.
Hum Mol Genet ; 24(22): 6417-27, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26358771

RESUMO

Arginase deficiency is caused by deficiency of arginase 1 (ARG1), a urea cycle enzyme that converts arginine to ornithine. Clinical features of arginase deficiency include elevated plasma arginine levels, spastic diplegia, intellectual disability, seizures and growth deficiency. Unlike other urea cycle disorders, recurrent hyperammonemia is typically less severe in this disorder. Normalization of plasma arginine levels is the consensus treatment goal, because elevations of arginine and its metabolites are suspected to contribute to the neurologic features. Using data from patients enrolled in a natural history study conducted by the Urea Cycle Disorders Consortium, we found that 97% of plasma arginine levels in subjects with arginase deficiency were above the normal range despite conventional treatment. Recently, arginine-degrading enzymes have been used to deplete arginine as a therapeutic strategy in cancer. We tested whether one of these enzymes, a pegylated human recombinant arginase 1 (AEB1102), reduces plasma arginine in murine models of arginase deficiency. In neonatal and adult mice with arginase deficiency, AEB1102 reduced the plasma arginine after single and repeated doses. However, survival did not improve likely, because this pegylated enzyme does not enter hepatocytes and does not improve hyperammonemia that accounts for lethality. Although murine models required dosing every 48 h, studies in cynomolgus monkeys indicate that less frequent dosing may be possible in patients. Given that elevated plasma arginine rather than hyperammonemia is the major treatment challenge, we propose that AEB1102 may have therapeutic potential as an arginine-reducing agent in patients with arginase deficiency.


Assuntos
Arginase/uso terapêutico , Arginina/sangue , Hiperargininemia/tratamento farmacológico , Animais , Arginase/sangue , Arginase/genética , Arginina/metabolismo , Encéfalo/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/metabolismo , Hiperargininemia/sangue , Hiperargininemia/genética , Hiperargininemia/metabolismo , Estudos Longitudinais , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/uso terapêutico , Convulsões/sangue , Convulsões/metabolismo
10.
Environ Health Perspect ; 123(12): 1255-64, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26032647

RESUMO

BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. METHODS: Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. RESULTS: The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. CONCLUSIONS: This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor ß activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.


Assuntos
Neoplasias da Mama/induzido quimicamente , Carcinógenos/toxicidade , Estrogênios/toxicidade , Mutagênicos/toxicidade , Bioensaio , Dano ao DNA , Feminino , Humanos , Projetos Piloto , Risco , Testes de Toxicidade
11.
Expert Rev Clin Pharmacol ; 7(2): 211-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24450420

RESUMO

Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose-response curves and can be lethal in children. A review of the purported mechanisms of action suggest hepatotoxicity results from increased oxidative stress, caused by a reduction in beta-oxidation and an increase in activation of certain metabolizing enzymes. There is also evidence that both carnitine and pantothenic acid are involved in the regulation of valproic acid-induced hepatotoxic processes, and clinical evidence has shown that treatment with either compound shows protective effects against hepatotoxicity. These results suggest a potential increase in protective effects with cotreatment of carnitine and pantothenic acid.


Assuntos
Carnitina/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ácido Pantotênico/uso terapêutico , Ácido Valproico/efeitos adversos , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Carnitina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Quimioterapia Combinada , Humanos , Estresse Oxidativo/efeitos dos fármacos , Ácido Pantotênico/administração & dosagem , Convulsões/tratamento farmacológico , Ácido Valproico/uso terapêutico
12.
Work ; 49(4): 641-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24004790

RESUMO

BACKGROUND: One hundred and sixty million office workers (knowledge workers) in the U.S. and 2/3 of the developed countries use computers on a daily basis. OBJECTIVE: Investigate the effectiveness of ergonomic and diversified chiropractic care for the reduction of pain, discomfort and impaired productivity in knowledge workers presenting with neck and upper extremity musculoskeletal complaints. METHODS: A one-year prospective case series (n=5 applying ergonomic job task analyses and ongoing surveillance at baseline, 8 weeks, 16 weeks and one-year for musculoskeletal discomfort (CMDQ and VAS, quality of life (Rand SF-36, productivity and forward head posture (FHP). RESULTS: CMDQ and VAS scores decreased by 45% (neck) and 80% (upper extremities); productivity increased from 65% to 100%; physical functioning, role physical and role emotional improved for 4 of 5 subjects; body pain and general health improved for 3 of 5. Average FHP changed from 1-inch (baseline) to 1/4-inch (16-weeks) to 1/2-inch (one year). CONCLUSIONS: Effectiveness of this intervention for the reduction of risks depended upon the subject's adoption of safe workstyle behaviors and postures. A transtheoretical model (TTM) for behavior change is discussed as a possible methodology to enhance the adoption of safer work habits.


Assuntos
Quiroprática , Ergonomia/métodos , Ensino , Extremidade Superior/lesões , Adulto , Computadores , Feminino , Humanos , Decoração de Interiores e Mobiliário/normas , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Postura/fisiologia , Estudos Prospectivos , Qualidade de Vida
13.
J Chiropr Med ; 12(1): 45-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23997724

RESUMO

OBJECTIVE: This report describes the case management of musculoskeletal disorders for an employee in a college work environment using both chiropractic care and applied ergonomics. CLINICAL FINDINGS: A 54-year-old male office worker presented with decreased motor function in both wrists; intermittent moderate-to-severe headaches; and pain or discomfort in the neck, both shoulders, left hand and wrist, and lumbosacral region resulting from injuries sustained during recreational soccer and from excessive forces and awkward postures when interacting with his home and office computer workstations. INTERVENTION AND RESULTS: Ergonomic training, surveillance, retrofitted equipment with new furniture, and an emphasis on adopting healthy work-style behaviors were applied in combination with regular chiropractic care. Baseline ergonomic job task analysis identified risk factors and delineated appropriate control measures to improve the subject's interface with his office workstation. Serial reevaluations at 3-month, 1-year, and 2-year periods recorded changes to the participant's pain, discomfort, and work-style behaviors. At end of study and relative to baseline, pain scale improved from 4/10 to 2/10; general disability improved from 4 to 0; and hand grip strength (pounds) increased from 20 to 105 (left) and 45 to 100 (right). Healthy work habits and postures adopted in the 3-month to 1-year period regressed to baseline exposures for 3 of 6 risk priorities identified in the ergonomic job task analysis. CONCLUSION: The patient responded positively to the intervention of chiropractic care and applied ergonomics.

14.
New Phytol ; 200(3): 767-777, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23869799

RESUMO

Disturbance affects most terrestrial ecosystems and has the potential to shape their responses to chronic environmental change. Scrub-oak vegetation regenerating from fire disturbance in subtropical Florida was exposed to experimentally elevated carbon dioxide (CO2) concentration (+350 µl l(-1)) using open-top chambers for 11 yr, punctuated by hurricane disturbance in year 8. Here, we report the effects of elevated CO2 on aboveground and belowground net primary productivity (NPP) and nitrogen (N) cycling during this experiment. The stimulation of NPP and N uptake by elevated CO2 peaked within 2 yr after disturbance by fire and hurricane, when soil nutrient availability was high. The stimulation subsequently declined and disappeared, coincident with low soil nutrient availability and with a CO2 -induced reduction in the N concentration of oak stems. These findings show that strong growth responses to elevated CO2 can be transient, are consistent with a progressively limited response to elevated CO2 interrupted by disturbance, and illustrate the importance of biogeochemical responses to extreme events in modulating ecosystem responses to global environmental change.


Assuntos
Dióxido de Carbono/metabolismo , Tempestades Ciclônicas , Ecossistema , Incêndios , Nitrogênio/metabolismo , Quercus/crescimento & desenvolvimento , Solo/química , Atmosfera , Biomassa , Florida , Ciclo do Nitrogênio , Caules de Planta/metabolismo , Quercus/metabolismo , Árvores/crescimento & desenvolvimento , Árvores/metabolismo
15.
PLoS One ; 8(5): e64386, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23717607

RESUMO

The effects of elevated CO2 on ecosystem element stocks are equivocal, in part because cumulative effects of CO2 on element pools are difficult to detect. We conducted a complete above and belowground inventory of non-nitrogen macro- and micronutrient stocks in a subtropical woodland exposed to twice-ambient CO2 concentrations for 11 years. We analyzed a suite of nutrient elements and metals important for nutrient cycling in soils to a depth of ~2 m, in leaves and stems of the dominant oaks, in fine and coarse roots, and in litter. In conjunction with large biomass stimulation, elevated CO2 increased oak stem stocks of Na, Mg, P, K, V, Zn and Mo, and the aboveground pool of K and S. Elevated CO2 increased root pools of most elements, except Zn. CO2-stimulation of plant Ca was larger than the decline in the extractable Ca pool in soils, whereas for other elements, increased plant uptake matched the decline in the extractable pool in soil. We conclude that elevated CO2 caused a net transfer of a subset of nutrients from soil to plants, suggesting that ecosystems with a positive plant growth response under high CO2 will likely cause mobilization of elements from soil pools to plant biomass.


Assuntos
Dióxido de Carbono/metabolismo , Quercus/metabolismo , Solo/química , Biomassa , Ecossistema , Metais/química , Metais/metabolismo , Fósforo/química , Fósforo/metabolismo , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Enxofre/química , Enxofre/metabolismo
16.
New Phytol ; 200(3): 753-766, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23718224

RESUMO

Rising atmospheric carbon dioxide (CO2) could alter the carbon (C) and nitrogen (N) content of ecosystems, yet the magnitude of these effects are not well known. We examined C and N budgets of a subtropical woodland after 11 yr of exposure to elevated CO2. We used open-top chambers to manipulate CO2 during regrowth after fire, and measured C, N and tracer (15) N in ecosystem components throughout the experiment. Elevated CO2 increased plant C and tended to increase plant N but did not significantly increase whole-system C or N. Elevated CO2 increased soil microbial activity and labile soil C, but more slowly cycling soil C pools tended to decline. Recovery of a long-term (15) N tracer indicated that CO2 exposure increased N losses and altered N distribution, with no effect on N inputs. Increased plant C accrual was accompanied by higher soil microbial activity and increased C losses from soil, yielding no statistically detectable effect of elevated CO2 on net ecosystem C uptake. These findings challenge the treatment of terrestrial ecosystems responses to elevated CO2 in current biogeochemical models, where the effect of elevated CO2 on ecosystem C balance is described as enhanced photosynthesis and plant growth with decomposition as a first-order response.


Assuntos
Dióxido de Carbono/metabolismo , Carbono/metabolismo , Meio Ambiente , Nitrogênio/metabolismo , Quercus/metabolismo , Microbiologia do Solo , Solo/química , Atmosfera , Ciclo do Carbono , Ecossistema , Incêndios , Ciclo do Nitrogênio , Fotossíntese , Quercus/crescimento & desenvolvimento , Árvores , Clima Tropical
17.
Expert Rev Clin Pharmacol ; 6(2): 185-95, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23473595

RESUMO

Adverse drug reactions continue to be a major cause of morbidity in both patients receiving therapeutics and in drug R&D programs. Predicting and possibly eliminating these adverse events remains a high priority in industry, government agencies and healthcare systems. With small molecule candidates, the fusion of nonclinical and clinical data is essential in establishing an overall system that creates a true translational science approach. Several new advances are taking place that attempt to create a 'patient context' mechanism early in drug research and development and ultimately into the marketplace. This 'life-cycle' approach has as its core the development of human-oriented, nonclinical end points and the incorporation of clinical knowledge at the drug design stage. The next 5 years should witness an explosion of what the author views as druggable and safe chemical space, pharmacosafety molecular targets and the most important aspect, an understanding of unique susceptibilities in patients developing adverse drug reactions. Our current knowledge of clinical safety relies completely on pharmacovigilance data from approved and marketed drugs, with a few exceptions of drugs failing in clinical trials. Massive data repositories now and soon to be available via cloud computing should stimulate a major effort in expanding our view of clinical drug safety and its incorporation into early drug research and development.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Simulação por Computador , Descoberta de Drogas/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Animais , Ensaios Clínicos como Assunto , Humanos
18.
Methods Mol Biol ; 930: 253-73, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23086845

RESUMO

Biomarkers are characteristics objectively measured and evaluated as indicators of: normal biologic processes, pathogenic processes, or pharmacologic response(s) to a therapeutic intervention. In environmental research and risk assessment, biomarkers are frequently referred to as indicators of human or environmental hazards. Discovering and implementing new biomarkers for toxicity caused by exposure to a chemical either from a therapeutic intervention or accidentally through the environment continues to be pursued through the use of animal models to predict potential human effects, from human studies (clinical or epidemiologic) or biobanked human samples, or the combination of all such approaches. The key to discovering or inferring biomarkers through computational means involves the identification or prediction of the molecular target(s) of the chemical(s) and the association of these targets with perturbed biological pathways. Two examples are given in this chapter: (1) inferring potential human biomarkers from animal toxicogenomics data, and (2) the identification of protein targets through computational means and associating these in one example with potential drug interactions and in another case with increasing the risk of developing certain human diseases.


Assuntos
Biomarcadores/metabolismo , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Determinação de Ponto Final , Redes Reguladoras de Genes , Humanos , Camundongos , Ratos
19.
J Manipulative Physiol Ther ; 34(4): 239-46, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21621725

RESUMO

OBJECTIVE: The purpose of this study was to quantify interexaminer reliability of a standardized supine leg check procedure used to screen for leg-length inequality. METHODS: Two doctors of chiropractic used a standardized supine leg check procedure to examine 50 volunteers for leg-length inequality. The order of examination was randomized. The side and magnitude of leg-length inequality were determined to the nearest 1/8 in. Subjects and examiners were blinded. Interexaminer reliability was assessed with a Bland-Altman plot, tolerance table of absolute differences, a quadratic weighted κ statistic for quantitative scores, and a Gwet's first-order agreement coefficient for dichotomous ratings. RESULTS: The quadratic weighted κ statistic to quantify the reliability of the rating scale was 0.44 (95% confidence interval, 0.21-0.67), indicating moderate reliability. The 2 examiners agreed exactly 32% of the time, within 1/8 in 58% of the time, within 3/16 in 72% of the time, and within 3/8 in 92% of the time. The Bland-Altman plot revealed possible heterogeneity in reliability that requires additional study. The examiners agreed on the presence of a leg-length inequality of at least 1/8 in in 40 (80%) of 50 subjects (first-order agreement coefficient, 0.76), suggesting good agreement for this diagnostic category. CONCLUSION: The examiners showed moderate reliability in assessing leg-length inequality at 1/8-in increments and good reliability in determining the presence of a leg-length inequality.


Assuntos
Desigualdade de Membros Inferiores/diagnóstico , Exame Físico/métodos , Exame Físico/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Decúbito Dorsal , Adulto Jovem
20.
Inflamm Bowel Dis ; 17(1): 15-21, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20629099

RESUMO

BACKGROUND: Clinical variables may identify a subset of patients with pediatric-onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric-onset UC. METHODS: We conducted a chart review of patients with pediatric-onset UC at a single center over a 10-year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy. RESULTS: Among 470 patients with inflammatory bowel disease ICD9-coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1- and 3-year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%-24.8%) and 35.6% (26.7%-45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively). CONCLUSIONS: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric-onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies.


Assuntos
Colectomia , Colite Ulcerativa , Adolescente , Criança , Estudos de Coortes , Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...