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1.
Phys Rev Lett ; 131(20): 202501, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38039485

RESUMO

The changes in mean-squared charge radii of neutron-deficient gold nuclei have been determined using the in-source, resonance-ionization laser spectroscopy technique, at the ISOLDE facility (CERN). From these new data, nuclear deformations are inferred, revealing a competition between deformed and spherical configurations. The isotopes ^{180,181,182}Au are observed to possess well-deformed ground states and, when moving to lighter masses, a sudden transition to near-spherical shapes is seen in the extremely neutron-deficient nuclides, ^{176,177,179}Au. A case of shape coexistence and shape staggering is identified in ^{178}Au which has a ground and isomeric state with different deformations. These new data reveal a pattern in ground-state deformation unique to the gold isotopes, whereby, when moving from the heavy to light masses, a plateau of well-deformed isotopes exists around the neutron midshell, flanked by near-spherical shapes in the heavier and lighter isotopes-a trend hitherto unseen elsewhere in the nuclear chart. The experimental charge radii are compared to those from Hartree-Fock-Bogoliubov calculations using the D1M Gogny interaction and configuration mixing between states of different deformation. The calculations are constrained by the known spins, parities, and magnetic moments of the ground states in gold nuclei and show a good agreement with the experimental results.

2.
Ecol Appl ; 30(3): e02058, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31838775

RESUMO

Most spatial conservation planning for wide-ranging or migratory species is constrained by poor knowledge of species' spatiotemporal dynamics and is only based on static species' ranges. However, species have substantial variation in abundance across their range and migratory species have important spatiotemporal population dynamics. With growing ecological data and advancing analytics, both of these can be estimated and incorporated into spatial conservation planning. However, there is limited information on the degree to which including this information affects conservation planning. We compared the performance of systematic conservation prioritizations for different scenarios based on varying the input species' distributions by ecological metric (abundance distributions versus range maps) and temporal sampling resolution (weekly, monthly, or quarterly). We used the example of a community of 41 species of migratory shorebirds that breed in North America, and we used eBird data to produce weekly estimates of species' abundances and ranges. Abundance distributions at a monthly or weekly resolution led to prioritizations that most efficiently protected species throughout the full annual cycle. Conversely, spatial prioritizations based on species' ranges required more sites and left most species insufficiently protected for at least part of their annual cycle. Prioritizations with only quarterly species ranges were very inefficient as they needed to target 40% of species' ranges to include 10% of populations. We highlight the high value of abundance information for spatial conservation planning, which leads to more efficient and effective spatial prioritization for conservation. Overall, we provide evidence that spatial conservation planning for wide-ranging migratory species is most robust and efficient when informed by species' abundance information from the full annual cycle.


Assuntos
Cruzamento , Conservação dos Recursos Naturais , América do Norte , Dinâmica Populacional
3.
Phys Rev Lett ; 120(14): 143002, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29694134

RESUMO

We have made precise measurements of the cyclotron frequency ratios H_{3}^{+}/HD^{+} and H_{3}^{+}/^{3}He^{+} and observe that different H_{3}^{+} ions result in different cyclotron frequency ratios. We interpret these differences as due to the molecular rotational energy of H_{3}^{+} changing its inertial mass. We also confirm that certain high J, K rotational levels of H_{3}^{+} have mean lifetimes exceeding several weeks. From measurements with the lightest H_{3}^{+} ion we obtain lower limits on the atomic masses of deuterium and helium-3 with respect to the proton.

5.
Arch Gynecol Obstet ; 297(4): 837-846, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29356953

RESUMO

BACKGROUND: Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330, 2009). RESULTS: PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669-678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy. CONCLUSIONS: Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Administração por Inalação , Aerossóis , Áustria , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasia Residual , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
6.
Eur J Clin Microbiol Infect Dis ; 34(8): 1559-66, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25934375

RESUMO

Invasive pneumococcal pneumonia is associated with high rates of mortality. Clinical assessment tools have poor sensitivity for predicting clinical outcomes. Molecular measurements of bacterial load correlate closely with clinical outcome but require specialist facilities and expertise. This study describes how routine blood culture testing can estimate bacterial load and predict clinical outcome for invasive pneumococcal pneumonia. Between December 2009 to March 2014, clinical and laboratory data were collected for 50 patients with Streptococcus pneumoniae bacteraemia secondary to community-acquired pneumonia. Fluorescence rates (FR) were calculated from growth curves generated by BACTEC blood culture analysers by dividing change in fluorescence units (FU), measured at the first point of detectable fluorescence and at the point of automated BACTEC positivity, by time in hours. The mean age of the patients was 70.6 years (49.6-86.3). Forty patients survived invasive pneumococcal disease and ten patients died. These two groups did not significantly differ by demographic or clinical characteristics. The mean FR for the non-survival group (3.62 × 10(-3) FU/h) was significantly higher (p < 0.001) than that of the survival group (1.73 × 10(-3) FU/h). FR did not vary by serotype. We determined that an FR of 2.59 × 10(-3) FU/h might represent a useful threshold for predicting high mortality risk with a sensitivity of 91 % and a specificity of 97 %. Our FR calculation uses cheap and accessible routine blood culture techniques to predict mortality in a small retrospective cohort study. In patients admitted to hospital with pneumococcal bacteraemia and, potentially, other organisms, this single tool could guide early escalation of clinical care.


Assuntos
Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Carga Bacteriana , Sangue/microbiologia , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
7.
Eur J Gynaecol Oncol ; 34(1): 23-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23589994

RESUMO

OBJECTIVE: Lower limb lymphedema (LLL) is a major cause of morbidity in patients with gynecological malignancies after surgical treatment involving lymph node (LN) dissection. The aim of this study was to estimate the prevalence of LLL in such patients and detect risk factors for its occurrence. MATERIALS AND METHODS: A retrospective analysis of all patients undergoing lymphadenectomy in newly-diagnosed gynecological malignancies at the University Hospital of Zurich between 2000 and 2007 was performed. Data from 313 patients were collected. Twenty patients with pre-existing edema or missing information were excluded before analysis. Time-to-LLL was estimated using the Kaplan-Meier estimate and potential risk factors were evaluated by a Cox regression model. RESULTS: Estimated prevalence of LLL one year after surgery was 32%, increasing to 58% eight years after surgery. Median time to diagnosis of LLL was 5.2 years. The number of removed lymph nodes was significantly associated with time-to-LLL. Diagnosis of postoperative lymphocysts and local infections were accompanied by a significantly elevated risk for the development of LLL. Furthermore, time-to-LLL decreased with a higher body mass index (BMI) of the patient. In contrast, chemo- and radiotherapy, age, positive LNs, site of lymphadenectomy, and type of cancer were not observed to be associated with the occurrence of LLL. CONCLUSIONS: LLL is a frequent postoperative complication in patients undergoing lymphadenectomy for gynecological malignancies. It is thus imperative to sufficiently educate patients about the risk and symptoms of LLL prior to surgery. The data clearly show an association between time-to-LLL and number of dissected LNs, stressing the need to prospectively analyze the prevalence of LLL and carefully plan LN sampling as increasing knowledge is gained regarding the therapeutic benefit of sentinel and systemic lymphadenectomy in patients with different stages of gynecological malignancies.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/efeitos adversos , Linfedema/epidemiologia , Feminino , Humanos , Extremidade Inferior , Linfedema/etiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco
8.
Gene Ther ; 19(11): 1107-13, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22089494

RESUMO

We previously reported regulated expression of erythropoietin (EPO) over 4 weeks in the peripheral nerve in vivo, using a herpes simplex virus (HSV)-based vector containing a Tet-on regulatable gene expression cassette. To create a vector that would be appropriate for the treatment of chronic neuropathy, we constructed a HSV vector with expression of EPO under the control of the Tet-on system in which the HSV latency-associated promoter 2 element was used to drive the expression of the Tet-on transactivator. EPO expression from the vector was tightly controlled by administration of doxycycline (DOX) in vitro. One month after inoculation of the vector to transduce dorsal root ganglion (DRG) in vivo, administration of DOX-containing chow-induced expression of EPO. Mice with streptozotocin-induced diabetes, inoculated with the vector, were protected against the development of neuropathy by continuous administration of DOX-containing chow over the course of 3 months. Identical results were achieved when DOX was administered every other week over 3 months of diabetes, but administration of DOX, 1 week out of 3, provided only partial protection against the development of neuropathy. Taken together, these results suggest such a vector is well suited for clinical trial for the treatment of chronic or subacutely developing neuropathy.


Assuntos
Proteínas de Ligação a DNA/genética , Eritropoetina/genética , Regulação da Expressão Gênica , Vetores Genéticos/genética , Proteínas de Membrana/genética , Regiões Promotoras Genéticas , Simplexvirus/genética , Animais , Linhagem Celular , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/terapia , Progressão da Doença , Doxiciclina/farmacologia , Eritropoetina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ordem dos Genes , Terapia Genética , Humanos , Masculino , Camundongos
9.
Gene Ther ; 19(1): 101-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21614028

RESUMO

Opiate/narcotic analgesics are the most effective treatments for chronic severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. Recent evidence suggests chronic morphine may activate glial cells to release proinflammatory cytokines. In this study, we used herpes simplex virus (HSV) vector-based gene transfer to dorsal root ganglion to produce a local release of p55 tumor necrosis factor (TNF) soluble receptor in the spinal cord in rats with morphine tolerance. Subcutaneous inoculation of HSV vectors expressing p55 TNF soluble receptor into the plantar surface of the hindpaws enhanced the antinociceptive effect of acute morphine in rats. Subcutaneous inoculation of those vectors into hindpaws also delayed the development of chronic morphine tolerance in rats. TNF soluble receptor expressed by HSV vector reduced gene transcription of spinal TNFα and interleukin-1ß (IL-1ß) induced by repeated morphine. Furthermore, we found that TNF soluble receptor mediated by HSV reversed the upregulation of protein level of TNFα and IL-1ß and phosphorylation of p38 mitogen-activated protein kinase induced by repeated morphine. These results support the concept that proinflammatory cytokines may have an important role in the pathogenesis induced by morphine. This study provides a novel approach to treating morphine tolerance.


Assuntos
Tolerância a Medicamentos , Morfina/farmacologia , Receptores do Fator de Necrose Tumoral/imunologia , Transgenes , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Comportamento Animal , Gânglios Espinais/imunologia , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Vetores Genéticos/metabolismo , Injeções Subcutâneas , Interleucina-1beta/imunologia , Masculino , Morfina/administração & dosagem , Fosforilação , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Simplexvirus/genética , Simplexvirus/imunologia , Simplexvirus/metabolismo , Medula Espinal/imunologia , Medula Espinal/metabolismo , Fatores de Tempo , Transcrição Gênica , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Gene Ther ; 19(9): 907-14, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22052241

RESUMO

We evaluated the therapeutic effect of erythropoietin (EPO) delivered by direct injection of a nonreplicating herpes simplex virus (HSV)-based vector coding for EPO (vEPO) in a model of cervical hemicord contusion at C7. At 1 h after spinal cord injury (SCI), either vEPO or control vector carrying a reporter gene (vC) was injected into the cord above and below the lesion. Animals injected with vEPO showed a statistically significant improvement in the ipsilateral forelimb function, as measured by open-field evaluation of motor performance, forelimb reaching in the cylinder test and misplacement in grid walk. This correlated with preservation of gray matter in the area of the lesion. There was also mild but significant improvement of hindlimb motor function measured by Basso-Beattie-Bresnahan score and computerized gait analysis in vEPO compared with control vector-injected animals. Microtubule-associated protein tau, phosphorylated and nonphosphorylated neurofilament protein and the synaptic proteins synaptophysin and PSD-95 were all significantly increased in the spinal cord of vEPO-treated animals compared with control vector-injected animals. These data suggest that gene transfer of EPO after cervical SCI by minimizing the injury size and enhancing tissue sparing preserves large-caliber axons and promotes synaptogenesis.


Assuntos
Contusões/terapia , Eritropoetina/genética , Vetores Genéticos , Simplexvirus/genética , Traumatismos da Medula Espinal/terapia , Transfecção , Animais , Feminino , Membro Anterior/fisiopatologia , Membro Posterior/fisiopatologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neurofilamentos/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal/citologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
11.
Phys Rev Lett ; 108(6): 062502, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22401059

RESUMO

The 110Pd double-ß decay Q value was measured with the Penning-trap mass spectrometer ISOLTRAP to be Q=2017.85(64) keV. This value shifted by 14 keV compared with the literature value and is 17 times more precise, resulting in new phase-space factors for the two-neutrino and neutrinoless decay modes. In addition a new set of the relevant matrix elements has been calculated. The expected half-life of the two-neutrino mode was reevaluated as 1.5(6)×10(20) yr. With its high natural abundance, the new results reveal 110Pd to be an excellent candidate for double-ß decay studies.

12.
Gynecol Oncol ; 125(3): 604-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22406639

RESUMO

OBJECTIVE: The aim of this study was to summarize the clinical experience at our clinic with pelvic exenteration as a treatment for cervical cancer with special regard to the indications and outcomes of specific patient groups. METHODS: Medical records of 282 women who underwent pelvic exenteration to treat cervical cancer were analyzed. RESULTS: In total, 70 patients (25%) underwent primary exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The overall survival (OS) of the 282 patients was 41% at 5 years and 37% at 10 years. The disease-free survival at 5 years was 61%. For 133 patients for whom pelvic exenteration was a curative procedure, the OS was 64% at 5 years and 57% at 10 years. For cases of pelvic exenteration as a palliative intervention, the OS was 19% at 5 years and 18% at 10 years. No difference was seen in the OS at 5 years between patients who received primary and secondary operations. No significant difference in the OS was found regardless of whether the patients had positive pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS was significantly lower. Out of all of the procedures, 139 (49%) involved no perioperative or postoperative complications. One major complication was reported for 72 (26%) patients, two complications occurred for 42 patients (15%) and more than three complications were noted for 29 (10%) patients. CONCLUSION: Pelvic exenteration is an effective technique with a high percentage of long-term survivors. To the best of our knowledge, our study involves the largest published number of patients treated with pelvic exenteration for a single gynecological cancer and shows that previous contraindications for pelvic exenteration, such as lymph node metastasis (especially when confined to the pelvic lymph nodes), older age or palliative intent, should be reconsidered.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Exenteração Pélvica/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
13.
Arch Gynecol Obstet ; 285(5): 1441-5, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22116315

RESUMO

PURPOSE: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. METHODS: 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. RESULTS: Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P = 0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P = 0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P = 0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P = 0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35 mm (±5.5 mm) and 8.4 mm (±3.4 mm), respectively. CONCLUSION: Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedure.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Conização/métodos , Eletrocirurgia/métodos , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Assistência Ambulatorial , Feminino , Humanos , Estudos Retrospectivos , Adulto Jovem
14.
Nat Med ; 3(3): 357-9, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9055868

RESUMO

HSV has a unique relationship with neurons which the virus naturally utilizes for efficient gene transfer and long-term gene expression. Progress in developing defective viral mutants with reduced cytotoxicity, and increasing insight into the state of the viral genome during latency and the functional elements of the latency promoter system, suggest that HSV vectors may be developed in which these natural features are exploited for effective transgene expression in brain.


Assuntos
Técnicas de Transferência de Genes , Vetores Genéticos , Neurônios , Simplexvirus , Animais , Engenharia Genética , Humanos
15.
Hamostaseologie ; 31 Suppl 1: S38-45, 2011 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-22057796

RESUMO

UNLABELLED: Electromyography (EMG) measures muscle electricity. It depends on muscle contraction and central motor control. Muscles react very sensitive on external signals (e. g. bleeding), The resulting changes can be shown in EMG. PATIENTS, METHODS: A first study included 51 children and young adults from Costa Rica. They underwent a clinical examination and EMG of the hip, knee and ankle joints. Resting muscle tone, maximal isometric contraction and three typical isotonic movements of the joints were measured. First step of analysis was to characterize typical pathogenic changes in the muscles and to find a corresponding physical therapy to minimize these changes. RESULTS: It showed that EMG is a good marker for muscle condition. It helps to individualize therapy and improve effectivity of physical and physiotherapeutic treatment of the locomotive system of children and young adults with hemophilia. It can help to recognize early subclinical changes and to control the outcome of therapeutic modalities.


Assuntos
Eletromiografia/métodos , Hemofilia A/diagnóstico , Hemofilia A/fisiopatologia , Contração Muscular , Músculo Esquelético/fisiopatologia , Doenças Musculares/diagnóstico , Doenças Musculares/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hemofilia A/terapia , Humanos , Masculino , Doenças Musculares/terapia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
J Small Anim Pract ; 62(3): 174-177, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33260253

RESUMO

OBJECTIVES: To evaluate if commercially available metronidazole and metronidazole benzoate suspensions cause a reduction in food intake in healthy chinchillas and if the reduction in food intake is dose-dependent. MATERIALS AND METHODS: Twelve chinchillas were used in a randomised, controlled, blinded, complete-crossover study. All treatments were administered orally every 12 hours for 3 days. Metronidazole (125 mg/mL) was administered at 20 mg/kg and metronidazole benzoate (25 mg/mL) was administered at 20 and 10 mg/kg. Food intake was recorded daily. The washout period between treatments was at least 14 days. RESULTS: At 20 mg/kg PO q12h administration of both commercial suspensions resulted in a significant reduction of food intake. The greatest mean reduction in food intake occurred after 2 to 3 days of drug administration (metronidazole: -54 ± 25%; metronidazole benzoate: -44 ± 36%). After administration of metronidazole benzoate at 10 mg/kg PO q12h, the reduction in food intake was significantly less pronounced (-24 ± 36%), suggesting that negative effect of metronidazole on food intake in chinchillas is dose-dependent. Variation in metronidazole-induced food intake reduction differed widely between individual chinchillas. CLINICAL SIGNIFICANCE: The oral administration of commercial metronidazole and metronidazole benzoate suspensions results in a dose-dependent clinically relevant reduction in food intake in chinchillas. Metronidazole should be used cautiously in this species and food intake should be monitored during treatment. Future studies are needed in order to determine if metronidazole at 10 mg/kg q12h is an effective therapeutic dosage in chinchillas.


Assuntos
Ingestão de Alimentos , Metronidazol , Administração Oral , Animais , Benzoatos , Chinchila , Estudos Cross-Over , Suspensões
17.
Isr J Health Policy Res ; 10(1): 53, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488859

RESUMO

BACKGROUND: Reimbursement for cardiac surgical procedures in Israel is uniform and does not account for diversity in costs of various procedures or for diversity in patient mix. In an era of new and costly technology coupled with higher risk patients needing more complex surgery, these tariffs may not adequately reflect the true financial burden on the caregivers. In the present study we attempt to determine whether case mix and complexity of procedures significantly affect cost to justify differential tariffs. METHODS: We included all patients undergoing cardiac surgery at Shaare Zedek Medical Center between the years 1993-2016. Patients were stratified according to (1) type of surgery and (2) clinical profile as reflected by the predicted operative risk according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE). Approximate cost of each group of patients was estimated by the average number of days in the Intensive Care Unit and days in the postoperative ward multiplied by the respective daily costs as determined by the Ministry of Health. We then added the fixed cost of the components used in the operating room (manpower and disposables). The final estimated cost (the outcome variable) was then evaluated as it relates to type of surgery and clinical profile. ANOVA was used to analyze cost variability between groups, and backward regression analysis to determine the respective effect of the abovementioned variables on cost. Because of non-normal distribution, both costs and lengths of stay were Log-transformed. RESULTS: Altogether there were 5496 patients: 3863, 836, 685 and 112 in the isolated CABG, CABG + valve, 1 valve and 2 valves replacement groups. By ANOVA, the costs in all EuroSCORE subgroups were significantly different from each other, increasing with increased EuroSCORE subgroup. Cost was also significantly different among procedure groups, increasing from simple CABG to single valve surgery to CABG + valve surgery to 2-valve surgery. In backward stepwise multiple regression analysis, both type of procedure and EuroSCORE group significantly impacted cost. ICU stay and Ward stay were significantly but weakly related while EuroSCORE subgroup was highly predictive of both ICU stay and ward stay. CONCLUSIONS: The cost of performing heart surgery today is directly influenced by both patient profile as well as type of surgery, both of which can be quantified. Modern day technology is costly yet has become mandatory. Thus reimbursement for heart surgery should be based on differential criteria, namely clinical risk profile as well as type of surgery. Our results suggest an urgent need for design and implementation of a differential tariff model in the Israeli reimbursement system. We suggest that a model using a fixed, average price according to the type of procedure costs, in addition to a variable hospitalization cost (ICU + ward) determined by the patient EuroSCORE or EuroSCORE subgroup should enable an equitable reimbursement to hospitals, based on their case mix.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Idoso , Envelhecimento , Humanos , Israel
18.
QJM ; 114(10): 699-705, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33165573

RESUMO

BACKGROUND: Early coronavirus disease 2019 (COVID-19) diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalizability. AIM: To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. DESIGN: A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19. METHODS: 581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data. RESULTS: The final multivariable model demonstrated AUC 0.8535 (95% confidence interval 0.8121-0.8950). The final model used six clinical variables that are routinely available in most low and high-resource settings. Using a cut-off of 2, the derived risk score has a sensitivity of 78.1% and specificity of 86.8%. At COVID-19 prevalence of 10% the model has a negative predictive value (NPV) of 96.5%. CONCLUSIONS: Our risk score is intended for diagnosis of COVID-19 in individuals admitted to hospital with suspected COVID-19. The score is the first developed for COVID-19 diagnosis using the TRIPOD checklist. It may be effective as a tool to rule out COVID-19 and function at different pandemic phases of variable COVID-19 prevalence. The simple score could be used by any healthcare worker to support hospital infection control prior to laboratory testing results.


Assuntos
COVID-19 , Teste para COVID-19 , Hospitais , Humanos , Estudos Retrospectivos , SARS-CoV-2
19.
J Exp Med ; 191(9): 1459-66, 2000 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-10790421

RESUMO

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8(+) T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8(+) T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8alpha monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8(+) T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8(+) T cells aborting virion production.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/crescimento & desenvolvimento , Neurônios Aferentes/virologia , Gânglio Trigeminal/virologia , Animais , Células Cultivadas , Infecções Oculares Virais/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Gânglio Trigeminal/citologia , Ativação Viral/imunologia , Latência Viral/imunologia
20.
Sci Rep ; 10(1): 16735, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028858

RESUMO

We report on engineering impact ionization characteristics of In0.53Ga0.47As/Al0.48In0.52As superlattice avalanche photodiodes (InGaAs/AlInAs SL APDs) on InP substrate to design and demonstrate an APD with low k-value. We design InGaAs/AlInAs SL APDs with three different SL periods (4 ML, 6 ML, and 8 ML) to achieve the same composition as Al0.4Ga0.07In0.53As quaternary random alloy (RA). The simulated results of an RA and the three SLs predict that the SLs have lower k-values than the RA because the electrons can readily reach their threshold energy for impact ionization while the holes experience the multiple valence minibands scattering. The shorter period of SL shows the lower k-value. To support the theoretical prediction, the designed 6 ML and 8 ML SLs are experimentally demonstrated. The 8 ML SL shows k-value of 0.22, which is lower than the k-value of the RA. The 6 ML SL exhibits even lower k-value than the 8 ML SL, indicating that the shorter period of the SL, the lower k-value as predicted. This work is a theoretical modeling and experimental demonstration of engineering avalanche characteristics in InGaAs/AlInAs SLs and would assist one to design the SLs with improved performance for various SWIR APD application.

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