Spread of common native and invasive grasses and ruderal trees following anthropogenic disturbances in a tropical dry forest

Introduction A fundamental challenge to the integrity of tropical dry forest ecosystems is the invasion of non-native grass species. These grasses compete for resources and fuel anthropogenic wildfires. In 2012, a bulldozer from the Puerto Rico Electric Power Authority cleared a 570-m trail from a state road into a mature dry forest section of Guánica Forest to control a wildfire. We monitored colonization by a non-native invasive grass (Megathyrsus maximus), a highly invasive tree (Leucaena leucocephala), and a native grass (Uniola virgata), as well as natural regeneration, along the bulldozer trail. We determined whether bulldozing facilitated colonization by these species into the forest and the extent of spread. Results Distance from propagule source and temporal variations strongly influenced colonization by our three focal species. Megathyrsus maximus invaded along the trail from source populations by the state road. The establishment of new colonies of M. maximus seedlings went as far as 570 m inside the forest (i.e., at the end of the bulldozer trail), but we found most new colonies within 270 m of the road. Leucaena leucocephala exhibited a similar spreading pattern. Before disturbance, Uniola virgata was distributed widely across the forest, but the highest densities were found in areas near the latter portion (\u3e 401 m) of the bulldozer trail. Subsequently, the species formed new clumps along more than half of the trail (250 to 570 m), apparently colonizing from undisturbed patches nearby. Conclusions Bulldozing facilitated the invasion of non-native vegetation. The projected community assemblage will be more fire-prone than before since M. maximus carries fire across the landscape better than U. virgata, emphasizing the capacity of invasive plant colonization to alter local ecological processes after only a single wildfire and bulldoze event. Our results provide a valuable baseline for short-term vegetation response to anthropogenic disturbances in tropical semi-deciduous dry forests

Suicide Pact

Objective: To determine the time of diagnosis of typical orofacial clefts in different Brazilian regions and its influence on age at surgical correction. Method: This was a prospective, descriptive, cross-sectional study conducted in medical centers in the Southeast, South, and Northeast of Brazil. Trained speech therapists and geneticists interviewed the parents of affected children using a previously validated questionnaire. Epi-Info and SPSS were used for data analysis. Significance level was set at 5% (p ≤ 0.05). Results: The sample consisted of 215 interviews conducted in the following regions: 21.9% (47) in the Southeast, 51.1% (110) in the South, and 27% (58) in the Northeast. Monthly family income was higher in the Southeast (p ≤ 0.05). Cleft lip and palate were found in 61.4% (132) of cases, cleft palate in 20.9% (45), and cleft lip in 17.7% (38). Diagnosis occurred in the maternity ward in 75.3% (162) of cases, during the prenatal period in 14% (30), and after hospital discharge in 10.2% (22). The Southeast had a higher frequency of prenatal diagnosis (27.7%), possibly related to greater purchasing power in this region and greater availability of prenatal investigation. Of all cases diagnosed in the maternity ward, 74.4% occurred in the Northeast. However, no significant difference was found when comparing time of diagnosis, region, and age at first surgery. Conclusion: Considering that diagnosis is more common in the maternity ward, local health care teams should be trained in order to effectively improve the initial care of these patients. Although time of diagnosis did not affect age at surgery, it favors the planning of neonatal care and treatment of affected infants. Copyright © 2011 by Sociedade Brasileira de Pediatria.873225230Wyszynski, D.F., (2002) Cleft Lip and Palate: From Origin to Treatment, , New York: Oxford University PressMoore, K.L., Persaud, T.V., The Pharyngeal (Branchial) Apparatus (1998) The Developing Human Clinically Oriented Embryology, pp. 215-256. , Moore KL, Persaud TV. 6th ed. Philadelphia, Pa: WB SaundersMossey, P.A., Little, J., Epidemiology of oral clefts: An international perspective (2002) Cleft Lip and Palate: from Origin to Treatment, pp. 127-158. , Wyszynski DF, editor. New York: Oxford University PressGlobal strategies to reduce the healthcare burden of craniofacial anomalies (2002) Report of WHO Meetings on International Collaborative Research on Craniofacial Anomalies, , Word Health Organization. Geneva: WHOStoll, C., Alembik, Y., Dott, B., Roth, M.P., Associated malformations in cases with oral clefts (2000) Cleft Palate-Craniofacial Journal, 37 (1), pp. 41-47Marazita, M.L., Mooney, M.P., Current concepts in the embryology and genetics of cleft lip and cleft palate (2004) Clin Plast Surg, 31, pp. 125-140Cohen Jr., M.M., Gorlin, R.J., Fraser, F.C., Craniofacial Disorders (1997) Emery and Rimoin's Principles and Practice of Medical Genetics, pp. 1121-1148. , Rimoin DL, Connor JM, Pyeritz RE, Korf BR, editors. New York: Churchill LivingstoneShprintzen, R.J., Siegel-Sadewitz, V.L., Amato, J., Goldberg, R.B., Anomalies associated with cleft lip, cleft palate, or both (1985) American Journal of Medical Genetics, 20 (4), pp. 585-595. , DOI 10.1002/ajmg.1320200404Offerdal, K., Jebens, N., Syvertsen, T., Blaas, H.G., Johansen, O.J., Eik-Nes, S.H., Prenatal ultrasound detection of facial clefts: A prospective study of 49,314 deliveries in a non-selected population in Norway (2008) Ultrasound Obstet Gynecol, 31, pp. 639-646Russell, K.A., Allen, V.M., MacDonald, M.E., Smith, K., Dodds, L., A population-based evaluation of antenatal diagnosis of orofacial clefts (2008) Cleft Palate-Craniofacial Journal, 45 (2), pp. 148-153. , DOI 10.1597/06-202.1Bunduki, V., Ruano, R., Sapienza, A.D., Hanaoka, B.Y., Zugaib, M., Diagnóstico pré-natal de fenda labial e palatina: Experiência de 40 casos (2001) RBGO, 23, pp. 561-566Grandjean, H., Larroque, D., Levi, S., The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study (1999) American Journal of Obstetrics and Gynecology, 181 (2), pp. 446-454. , DOI 10.1016/S0002-9378(99)70577-6Amstalden-Mendes, L.G., Magna, L.A., Gil-da-Silva-Lopes, V.L., Neonatal care of infants with cleft lip and/or palate: Feeding orientation and evolution of weight gain in a nonspecialized Brazilian hospital (2007) Cleft Palate-Craniofacial Journal, 44 (3), pp. 329-334. , DOI 10.1597/05-177Reid, J., A review of feeding interventions for infants with cleft palate (2004) Cleft Palate-Craniofacial Journal, 41 (3), pp. 268-278. , DOI 10.1597/02-148.1Shaw, W.C., Semb, G., Nelson, P., Brattström, V., Molsted, K., Prahl- Andersen, B., The Eurocleft Project 1996-2000: Overview (2001) J Cranio-maxillofacial Surgery, 29, pp. 131-140Chitty, L.S., Griffin, D.R., Anormalidades do lábio e do palato fetal: Diagnóstico ultra-sonográfico (2005) Tratamento de Fissura Labial e Fenda Palatina, pp. 107-116. , Watson AC, Sell DA, Grunwell P. São Paulo: Editora SantosHabel, A., O papel do pediatra (2005) Tratamento de Fissura Labial e Fenda Palatina, pp. 123-135. , Watson AC, Sell DA, Grunwell P. São Paulo: Editora SantosRibeiro-Roda, S., Gil-da-Silva-Lopes, V.L., Aspectos odontológicos das fendas labiopalatinas e orientações para cuidados básicos (2008) Rev Cienc Med, 17, pp. 95-103Monlleo, I.L., Gil-da-Silva-Lopes, V.L., Craniofacial anomalies: Description and evaluation of treatment under the Brazilian Unified Health System (2006) Cadernos de Saude Publica, 22 (5), pp. 913-922. , http://www.scielo.br/pdf/csp/v22n5/04.pdfLoffredo, L.C., Freitas, J.A., Grigolli, A.A., Prevalência das fissuras orais de 1975 a 1994 (2001) Rev Saude Publica, 35, pp. 571-575Nunes, L.M., Queluz, D.P., Pereira, A.C., Prevalência de fissuras labiopalatais no município de Campos dos Goytacazes-RJ, 1999-2004 (2007) Rev Bras Epidemiol, 10, pp. 109-116Cerqueira, M.N., Teixeira, S.C., Naressi, S.C., Ferrreira, A.P., Ocorrência de fissuras labiopalatais na cidade de São José dos Campos-SP (2005) Rev Bras Epidemiol, 8, pp. 161-166Di Ninno, C.Q., Santos, P.G., Bueno, M.G., Syrio, I.M., A influência da época do diagnóstico das fissuras labiopalatinas (2006) Rev Soc Bras Fonoaudiol, 11, pp. 75-81Jones, M.C., Prenatal diagnosis of cleft lip and palate: Detection rates, accuracy of ultrasonography, associated anomalies and strategies for counseling (2002) Cleft Palate Craniofac J, 39, pp. 169-173Johnson, N., Sandy, J.R., Prenatal diagnosis of cleft lip and palate (2003) Cleft Palate-Craniofacial Journal, 40 (2), pp. 186-189. , DOI 10.1597/1545-1569(2003)0402.0.CO;2Bradbury, E., Bannister, P., Aconselhamento pré-natal, perinatal e pós-natal (2005) Tratamento de Fissura Labial e Fenda Palatina, pp. 117-122. , Watson AC, Sell DA, Grunwell P. São Paulo: Editora SantosDi Ninno, C.Q., Gomes, R.O., Santos, P.G., Bueno, M.G., Galvão, D.A., Meira, A.L., O conhecimento de profissionais da área da saúde sobre fissura labiopalatina (2004) Rev Soc Bras Fonoaudiol, 9, pp. 93-101Schardosim, L.R., Nogueira, D.A., Bosco, V.L., Pereima, M.J., Bebês portadores de fissura labiopalatal: Satisfação dos pais com as orientações recebidas dos profissionais (2004) JBP Rev Ibero-am Odontopediatr Odontol Bebe, 7, pp. 568-573Amstalden-Mendes, L.G., Gil-da-Silva-Lopes, V.L., Fenda de lábio e ou palato: Recursos para alimentação antes da correção cirúrgica (2006) Rev Cienc Med, 15, pp. 437-448. , CampinasVieira, G.O., Martins, C.C., Vieira, T.O., De Oliveira, N.F., Silva, L.R., Factors predicting early discontinuation of exclusive breastfeeding in the first month of life (2010) J Pediatr, 86, pp. 441-444. , Rio

Imposed registries within the European postmarketing surveillance system: Extended analysis and lessons learned for regulators

Purpose: Building on previous research, we examined whether delayed study start and low patient accrual rates found in 31 postauthorization registry-based studies requested by European Medicines Agency (EMA) are maintained after 2 additional years of follow-up. Method: The registries identified in the previous EMA study and the same methodology were used. The follow-up was extended from June 2015 to November 2017. The information available for the following variables was updated: marketing authorization status, study and registry status, study end date, planned duration, number of patients planned to be enrolled, and actual patients enrolled. Data were collected from several nonpublic in-house sources such as the study protocols, interim and final study reports, risk management plans, and periodic safety update reports. Results: As of November 2017, 10 (32.2%) studies were finalized (vs. 9.7% as of June 2015), 14 (45.2%) were still ongoing (vs. 64.5%). Four of the ongoing studies had patients' accrual lower than 50%. Six of the finalized studies had a delayed completion, with a median delay of 3 years. As of November 2017, the median patients' accrual percentages were 24% for ongoing studies (vs. 8.5%) and 101% for finalized studies (vs. 24%). Conclusion: Overall, the rate of recruitment and timely finalization were improved after 2 years of additional follow-up but show that further work is needed to facilitate use of registry data for regulatory purposes, a work that has started via the EMA registry initiative

Quantum linearization attacks

Recent works have shown that quantum period-finding can be used to break many popular constructions (some block ciphers such as Even-Mansour, multiple MACs and AEs...) in the superposition query model. So far, all the constructions broken exhibited a strong algebraic structure, which enables to craft a periodic function of a single input block. Recoverin

MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study

Objective: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. Methods: eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. Results: patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. Conclusions: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. Classification of evidence: this study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab

Building the cosmic distance scale: from Hipparcos to Gaia

Hipparcos, the first ever experiment of global astrometry, was launched by ESA in 1989 and its results published in 1997 (Perryman et al., Astron. Astrophys. 323, L49, 1997; Perryman & ESA (eds), The Hipparcos and Tycho catalogues, ESA SP-1200, 1997). A new reduction was later performed using an improved satellite attitude reconstruction leading to an improved accuracy for stars brighter than 9th magnitude (van Leeuwen & Fantino, Astron. Astrophys. 439, 791, 2005; van Leeuwen, Astron. Astrophys. 474, 653, 2007). The Hipparcos Catalogue provided an extended dataset of very accurate astrometric data (positions, trigonometric parallaxes and proper motions), enlarging by two orders of magnitude the quantity and quality of distance determinations and luminosity calibrations. The availability of more than 20000 stars with a trigonometric parallax known to better than 10% opened the way to a drastic revision of our 3-D knowledge of the solar neighbourhood and to a renewal of the calibration of many distance indicators and age estimations. The prospects opened by Gaia, the next ESA cornerstone, planned for launch in June 2013 (Perryman et al., Astron. Astrophys. 369, 339, 2001), are still much more dramatic: a billion objects with systematic and quasi simultaneous astrometric, spectrophotometric and spectroscopic observations, about 150 million stars with expected distances to better than 10%, all over the Galaxy. All stellar distance indicators, in very large numbers, will be directly measured, providing a direct calibration of their luminosity and making possible detailed studies of the impacts of various effects linked to chemical element abundances, age or cluster membership. With the help of simulations of the data expected from Gaia, obtained from the mission simulator developed by DPAC, we will illustrate what Gaia can provide with some selected examples.Comment: 16 pages, 16 figures, Conference "The Fundamental Cosmic Distance scale: State of the Art and the Gaia perspective, 3-6 May 2011, INAF, Osservatorio Astronomico di Capodimonte, Naples. Accepted for publication in Astrophysics & Space Scienc

Ozanimod in relapsing multiple sclerosis : Pooled safety results from the clinical development program

Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data. Methods: We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data. Results: At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE. Conclusions: Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis : Up to 5 years of follow-up in the DAYBREAK open-label extension trial

Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. Objective: To characterize long-term safety and efficacy of ozanimod. Methods: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. Results: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. Conclusions: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity