Sclerotinia sclerotiorum populations from tropical agricultural zones have been suggested to be more variable compared to those from temperate zones. However, no data were available comparing populations from both zones using the same set of markers. In this study, we compared S. sclerotiorum populations from the United States of America  and southeast Brazil  using the frequency of mycelial compatibility groups (MCGs) and 13 microsatellite (SSR) markers. Populations were sourced from diseased plants within leguminous crops in New York, USA , and Minas Gerais State, Brazil . Twenty MCGs were identified in NY and 14 were previously reported in MG. The effective number of genotypes based on Hill’s number of order 0, which corresponded to the number of multilocus genotypes (MLGs) were 22 (95% CI = 15.6–28.4) and 24 (95% CI = 18.9–29.1) in NY and MG, respectively. Clonal fractions of MLGs were 71.8% (NY) and 78.0% (MG). The effective number of genotypes based on Hill’s number of orders 1 and 2 in NY were 8.9 (95% CI = 5.2–12.6) and 4.4 (95% CI = 2.6–6.1), respectively. For MG these indices were 11.4 (95% CI = 8.7–14.1) and 7.1 (95% CI = 5.1–9.0), respectively. There were no significant differences of allelic richness, private allelic richness, gene diversity, effective number of alleles and genotype evenness between the NY and MG populations. The populations were differentiated, with 29% of total variance attributed to differences between them and G''ST and Jost’s D indices higher than 0.50. Cluster analysis revealed dissimilarity higher than 80% among most MLGs from both populations. Different alleles segregated in the populations but both had similar levels of genotypic variability. Sclerotinia sclerotiorum is amongst the most devastating and recalcitrant plant pathogens that infect a broad range of hosts and may lead to substantial crop losses  . Based opoppr package [In addition to genotypic diversity, the modified Hill’s ratio E5 evenness index was also calculated . Evennes package .rD index was calculated from clone-corrected data set using 999 permutations to estimate the linkage disequilibrium across the SSR loci. Linkage disequilibrium between all pairs of locus was also tested using MULTILOCUS program [rD index were also calculated using the poppr package [Genotype accumulation curves were produced for each population using 1,000 resamplings. The  program  and 1,00 package .ST [ST and Jost’s D range from zero (no differentiation) to one (complete differentiation). These indices were selected because they use different principles to measure genetic differentiation. G''ST index varies with the diversity within populations, while Jost’s D is based on the effective number of alleles [poppr package [The partitioning of variation between and within the populations was assessed by a hierarchical analysis of molecular variance (AMOVA) from the clone-corrected data set using the Arlequin program . The disST  and the ST  indices  alleles . A dissi package  was usedS. trifoliorum isolates was not amplified  to five (locus 114–4). In MG, the number of alleles ranged from two (locus 110–4) to nine (locus 114–4) . There wThe genotypic richness assessed by Hill’s number of order 0 (N0) of both populations was similar . In NY, No MLG was shared between NY and MG. The most frequent MLG in the NY population was detected in 35 isolates . In MG, D index in both populations was significantly different from zero (P > 0.05), while in MG, this proportion was equal to 45% (data not shown).The overall rrom zero . HoweverST index depicted a high level of genetic differentiation (G''ST = 0.75) and ranged from zero (locus 9–2) to 0.98 (locus 55–4). This was corroborated by the magnitude of the Jost’s measure of differentiation (D = 0.58), which ranged from zero (locus 9–2) to 0.95 (locus 55–4) (The G''us 55–4) . AMOVA ius 55–4) .Sclerotinia sclerotiorum populations from a tropical climatic zone  and a temperate zone  exhibited similar level of genetic diversity when two markers were used: frequency of MCGs and SSR markers. Despite the larger sample size of the MG population, the number of MCGs was smaller than in the NY population. Consequently, the clonal fraction in MG (87.2%) was higher than in the NY population (74.4%). This finding is consistent with earlier estimates of MCG diversity in S. sclerotiorum populations. Clonal fractions of MCGs in previous studies from temperate regions ranged from 34.4% [S. sclerotiorum from tropical zones.om 34.4%  to 90.1%on in MG 7.2% was on in MG 7.2% was om 34.4% ,13,15,17om 34.4% . Direct The distribution of MCGs frequencies in the two populations were similar, but were slightly different for the MLGs. In NY, only one MLG was present at high frequency (> 25 isolates). In MG, two MLGs (MLG1 and 2) in high frequency were identified. We reconstructed the MLGs histogram in MG summing the frequency of MLGs 1 and 2, which resulted in a similar frequency to that observed in NY  inset. TS. sclerotiorum populations from tropical zones could be linked to the higher number of generations of the pathogen associated with the availability of host crops throughout the year and consequently higher genetic variability. In the present study, both populations exhibited at least 40% of pairs of loci in linkage equilibrium. Moreover, in both populations there was a decoupling between MCGs and SSR markers. In the NY population, six MLGs were associated with more than one MCG, while in MG this occurred for one MLG. Linkage equilibrium between pairs of loci and unlinking of markers suggest the involvement of some recombination process [S. sclerotiorum genome. Therefore, a further study using higher-resolution genomic tools or the use of additional markers may provide further insight into the differential contribution of recombination in S. sclerotiorum populations from distinct climatic zones.Higher variability in  process  in both S. sclerotiorum populations from NY and MG were highly differentiated (G''ST or Jost’s D > 0.5) at eight of the 13 SSR loci. Populations from widely separated areas, a subtropical region of China (n = 30) and a temperate region of the USA (n = 29), were also highly differentiated at SSR loci [The Sclerotinia sclerotiorum populations from tropical and temperate zones exhibited substantial (> 70%) clonality. Several studies from different geographic regions have reported clonality in S. sclerotiorum populations [S. sclerotiorum populations tend to be panmictic (random mating). This has important implications for the development of management strategies, because pathogen populations in which random mating takes place tends to evolve faster [ulations ,9,17,18.ulations ,14,44,46e faster . Conseque faster . Here, tS1 FigSclerotinia sclerotiorum isolates.The amplification of DNA fragments of 100 base pairs (bp) is specific to (TIF)Click here for additional data file.S2 FigThe N0, N1 and N2 numbers correspond to genotype richness, the exponential of Shannon’s entropy, and the inverse of the Simpson’s concentration indices, respectively. Solid lines correspond to rarefaction (interpolation) and dashed lines to extrapolation curves. The 95% confidence intervals were obtained by a bootstrap method based on 200 replications.(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


The aim of this study was to report feasibility, the visual outcomes and complications of pediatric cataract surgery with primary intraocular lens implantation in children aged 5 to15 years in local anesthesia. This retrospective interventional case series included 62 eyes from 50 children who underwent pediatrc cataract surgery with primary intraocular lens implantation at the Mana eye Clinic Nkongsamba between 2006 and 2015 Main outcome measures were: best-corrected post operative visual acuity, and intraoperative and postoperative complications. Mean age at surgery was 10.18 ± 3.21 years. Mean follow up length was 15.75 ± 3.36 weeks. Etiology included: 10 congenital cataracs (16.12%). 35 developmental cataracts (56.45%) and 17 traumatic cataracts (27.41%). The mean preoperative BCVA was logMAR 1.19 ± 0.33. (range 0.6-2.3). After cycloplegia refraction 2 weeks after surgery, the mean postoperative BCVA was log MAR 0.58 ± 0.88 ( range 0.5-1.8). The mean implanted IOL power was 22.01 ±3.16 D. IOL was succefuly implanted in 54 eyes (87.07%). Eight eyes (9.67%) were left aphakic. Increase in BCVA of 4 logMAR lines and above was recorded in 27 patients (43.55%). Intraoperative complications included: 4 posterior capsule holes with vitrous lost, 3 lenses subluxation and 1 case of iris dialyse. Late postoperative complications included: posterior capsular opacity which occurred in 16 patients, 3 posterior synechia, 2 retinal detachment. Peribulbar anaesthesia can be considered as a viable option in selected patients presenting developmental cataract undergoing cataract surgery in developing countries. Effort should be made to improve the early identification of congenital cataract and its early surgical intervention and prompt optical rehabilitation to prevent amblyopia. Cataract is a common cause of childhood blindness , 2. The The medical charts and operation protocols of all children diagnosed with cataract who underwent cataract surgery with IOL implantation at the Mana Eye Clinic Nkongsamba between 2007 and 2015 were retrospectively reviewed. This research was approved by the local ethics committee. (Protocol 020/16). Prior to surgery, written informed consent was obtained from all parents or legal relatives after receiving an explanation of the nature of the procedure. Demographic parameters  and clinical characteristics , intraocular pressure (IOP), type of surgery, power of the implanted IOL, pre- and postoperative complications and compliance for follow-up visits) were analysed. The BCVA was tested on a Snellen chart and was converted to the logarithm of the minimum angle of resolution (logMAR) for statistical purposes. Non-numerical vision was arbitrary assigned a logMAR value So, counting finger (CF) = logMAR 1.70, hand motion (HM) = logMAR 2.00 intact light perception = logMAR 2.30, defect light perception = logMAR 2.70, and no light perception (NLP) = logMAR 3.00. The IOP was measured with an eye care tonometer. Strabismus was checked using alternate cover testing. Biomicroscopy was carried out before dilatation. A dilated fundus examination was done with a direct or indirect ophthalmoscope. Cataracts that impeded the vision of the red reflex at the ocular fundus examination were considered as total. These patients underwent a B-scan sonography to assess the retinal status. A patient was classified as having a congenital cataract if a cataract was noticed before the age of 1 year or a presence of strabismus or nystagmus was observed. All other non traumatic cases were considered as developmental cataract.Exclusion criteria included active uveitis, 360-degree posterior synechia, glaucoma, mental retardation, non cooperation with local anaesthesia and no concrete light projection. The IOL power was calculated using the Holliday II formula based on axial length (A-Scan) and keratometry readings. Depending on the age of the child, a specific amount of undercorrection to determine the power of the implanted IOL was done according to Dahan et al  who recoPositive psychological preparation of the patient was mandatory. The presence of the parents, from the consulting room to the operating room, was required. In our eye clinic, the following two standard operation techniques are used for paediatric cataract surgery under local anaesthesia according to the availability of IOLs: small incision cataract surgery (SICS) and manual phaco aspiration (MPA). The SICS was performed as described in the literature . The MPAFollow-up visits were scheduled as follows: 1 day, 7 days, 2 weeks, 12 weeks, 24 weeks and 52 weeks. At the first week follow-up visit, patients were examined on slit lamp to exclude any early complications. At the end of the second week, patients were submitted to cycloplegic refraction to assess the BCVA. All patient who did not improved at least two logMAR lines in BCVA in the absence of any surgical complication, were suspected of having amblyopia. They were referred for adequate management. In later visits, the posterior capsule status and other late complications were assessed. Patients who developed a posterior capsule opacification (PCO) were scheduled for a surgical posterior capsulotomy.Quantitative variables did not deviate significantly from the normal distribution; thus their values were reported as mean±standard deviation (SD). As results all tests carried out were parametric. Qualitative variables were presented in percent (%). Student’s paired t-test was carried out to compare post-operative and pre-operative visual acuity (VA). The analysis was performed using statistical software Epi-Info 7, IBM-SPSS 21, and R version 3.2.3. Since some expected frequencies were less than 5, Fisher’s exact test was used as measure of association. The Cochran–Armitage test for trend was used for ordinal categories. Odd ratios with 95% confidence interval (OR95%CI) were used for quantifying the associations. P-values less than 0.05 were considered statistically significant.A total of 62 consecutive children from 5 to 15 years old underwent cataract surgery at the Mana Eye Clinic Nkongsamba between 2007 and 2015 under local anaesthesia. There were 33 males (53.22%) and 29 females (46.78%). The mean age at surgery was 10.18 ± 3.21. Our patients mostly originated from the Littoral region (43.58%). The details of patient demographic and clinical characteristics are summarised in Biometry was done in 47 patients (75.80%). After undercorrection of 10%, the mean implanted IOL power was 22.01 ± 3.169. MPA was performed in 40 eyes (64.51 %), and 22 eyes (35.48%) underwent SICS. In 54 eyes, a posterior chamber IOL (48 in the capsule bag and 6 in the ciliar sulcus) was implanted (87.09%). Eight eyes (12.91%) were left aphakic. Primary posterior capsulotomy was performed in 33 eyes (53.22%). Preoperatively, all patients were blind in the affected eye. The mean BCVA (logMAR) increased significantly from 1.19 ± 0.93 preoperative to 0.58 ± 0.88 post-operative (p=0.000) . The posCataract is the leading cause of childhood blindness in Africa . Early sIn our series, primary IOL implantation was performed in 54 eyes (87.09%). The mean VA increased significantly from logMAR1.19 ± 0.33 preoperative to logMAR0.58 ± 0.88 postoperative (p = 0.000). Nystagmus was present in 16.12 % of patients before the surgery. It is a predictive factor for poor postoperative VA . Delay oThe retrospective character constitutes a serious limitation to our study. Necessary information was not recorded in some files; therefore, the classification to congenital cataract was only based on clinical findings, such as nystagmus. We could not comment on the visual outcome of children suspected for amblyopia due to the fact that postoperative management of amblyopia was carried out in another hospital. The final visual outcome of some patients could have been affected because they were given a standard IOL.Our results suggest that pediatric cataract surgery can be done under local anaesthesia on selected patients presenting developmental cataract. In cases of congenital cataract, early surgical intervention and prompt optical rehabilitation is mandatory to prevent irreversible deprivational amblyopia. Creation of well-equipped and well-staffed centres for the treatment of paediatric cataracts should be a priority for decision makers in the developing world.Pediatric cataracts are a common cause of childhood blindness;Pediatric cataract surgery must be done under general anesthesia.Our study reports the use of local anesthesia in pediatric cataract surgery;It also highlights the need of well staffed and well equipped centers for pediatric surgery in developing countries;


Q parameter for the beam quality and the ionization chamber type under investigation. The %dd(10)x of the Varian TrueBeam 2.5 MV imaging beam falls outside the range of the available data for the calculation of the kQ value. Due to the similarities of the 2.5 MV imaging beam and the 60Co beam, we and others made the assumption that kQ = 1.0 in TG51 calculations. In this study, we used the TG21 and TG51 calibration protocols in conjunction to validate that kQ = 1.0 for the 2.5 MV imaging beam using a PTW 30013 farmer chamber. Standard measurements for TG51 absolute dosimetry QA were performed at 100 cm SSD, 10 cm depth, 10 × 10 field size, delivering 100 Monitor Units to a waterproof Farmer Chamber (PTW TN30013) for both 2.5 and 6 MV. Both the TG21 and TG51 formalisms were used to calculate the dose to water per MU at dmax (Dw/MU) for the 6 MV beam. The calculated outputs were 1.0005 and 1.0004 cGy/MU respectively. The TG21 formalism was then used to calculate (Dw/MU) for the 2.5 MV imaging beam. This value was then used in the TG51 formalism to find kQ for the 2.5 MV imaging beam. A kQ value of 1.00 ± 0.01 was calculated for 2.5 MV using this method.AAPM Report 142 recommends and the State of Ohio requires that the imaging dose be quantified in radiotherapy applications. Using the TG51 dose calibration protocol for MV Imaging dose measurement requires knowledge of the k The absorbed‐dose‐to‐water factor, ND,w60Co, based on the TG51 protocol uses a kQ factor which converts the calibration factor for a 60Co beam quality, for which the absorbed‐dose calibration factor is applicable, to a clinical beam quality of Q. In the TG51 protocol, kQ values are provided in a figure and also tabulated for a variety of cylindrical chambers and beam qualities which are defined as the %dd(10)x. The later published Addendum to TG51Q for clinical beams of quality with %dd(10)x in the range of 63% to 86% and also provides kQ values for some newer ionization chambers such as PTW TN30013 .AAPM Report 142At our institution, we have Varian TrueBeam linear accelerators with 2.5 MV imaging beams. In an effort to meet the requirement of the ODH and to be able to characterize the dose given to patients during imaging with this beam, we set out to perform the dose quantification of the 2.5 MV imaging beam.Q must be known when using the TG51 formalism. We initially performed the calibration of this beam using the TG51 protocol with an assumed kQ value of 1.0. A recently published paper by Gräfe et al.Q of 1.0, using the 2.5 MV imaging beam and 0.64 cc Exradin A12  ionization chamber.In order to have an accurate output measurement, kQ = 1.0 for the 2.5 MV imaging beam under consideration with the PTW TN30013 ionization chamber, we performed the calibration of the 2.5 MV with the older TG21 formalism, which does not require any knowledge of kQ. The aim of this study is to use the TG21 protocol for the absolute dosimetry calculation for the 2.5 MV beam to validate the assumed value for kQ to be used in a TG51 protocol absolute dosimetry calibration.In order to validate our assumption of k60Co and 6 MV photon beams respectively. Tailor et al.60Co beam energy and decreasing with increasing photon energy.Two previous studies have compared the doses calculated by the TG21 and TG51 protocols for megavoltage beam dosimetry. Cho et al.2x for 2.5 MV is 51.53%. This is shown in Fig. x as shown in fig. 4 of the TG51 report or the empirical formula valid range as given in eq. 2 field size with a PTW waterproof farmer chamber (TN30013) to calculate Pion. The exposure calibration factor, Nx, and cavity‐gas factor, Ngas, were taken from the ADCL calibration certificate of the ionization chamber used and were verified against a calculated value of Ngas, using eq. wall was calculated using the mass stopping power ratio, L/ρ, and mean mass energy absorption coefficient, μen/ρ, listed in the TG21 formalism for the wall material, acrylic, based on specifications from the manufacturer .We measured the percentage depth dose (PDD) of the 2.5 MV imaging beam of a Varian TrueBeam linear accelerator with a CC13  detector in a cylindrical 3D Scanner water tank  for a 10 × 10 cm field size at 100 cm SSD. Our measured %dd(10)In TG21 protocol, the dose to water is given byAnd2. Prepl was taken as 0.992 by using fig. 5 of the TG21 protocol. The factors and parameter values used in the TG21 calibration are listed in Tables The fraction of ionization due to electrons from the chamber wall, α, was taken as zero using Fig. gas by using eq. gas are shown in Table We calculated NW/MU)TG21 at the calibration dosimetry conditions using the TG21 protocol, we equated the calculated value to the TG51 equation used to calculate (DW/MU) for the same reference geometry and solved for kQ as shown in eqs. After calculating  are accurate.We calculated the absorbed dose ratio at the reference conditions as (TG51/TG21)Q value was calculated as 1.0002 (Table Next, by calculating the absorbed dose of the 2.5 MV imaging beam with the TG21 formalism and solving eq. 02 Table .4Q value of 1.0002 for the 2.5 MV TrueBeam imaging photon beam using the PTW TN30013 ionization chamber. This value is within 0.02% of our and Gräfe et al.'s assumed kQ = 1.0. With up to ±1% difference shown60Co to 18 MV photon energies, we assigned a 1% uncertainty in our calculation of kQ. The use of a kQ = 1.000 is adequate for the 2.5 MV imaging photon beam using the PTW TN30013 ionization chamber to characterize the imaging beam dose.The method outlined yielded a kThe authors have no conflicts of interest relevant to the content of this article.


Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC). The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort.Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant (LT), HBV or HIV co-infection at presentation were analyzed (N = 1007). Outcomes included: 1) fibrosis progression 2) hepatic decompensation 3) HCC and 4) LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years.The external cohort had a median age of 49.4 years (IQR 44.3–54.3); 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2–7.6). Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2–7.6). Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC) for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73–0.83) and 0.76 (95% CI 0.69–0.81).Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases. Chronic liver disease remains one of the top 10 causes of death worldwide The clinDespite the marked improvement in efficacy and side effect profile of direct-acting antiviral agents (DAAs), chronic hepatitis C (CHC) remains a major public health problem due to the enormity of the worldwide disease burden, and the high proportion of chronically infected patients who have not been diagnosed or who do not have access to care., 7, 8 AlWe previously demonstrated that using longitudinal data from the Hepatitis C Antiviral Therapy to Prevent Cirrhosis (HALT-C) trial database accurate risk assessments for both fibrosis progression and clinical outcomes could be obtained for patients with CHC using only data routinely obtained in clinical practice., 5 HowevThe prediction models were initially constructed using 1050 patients in the HALT-C study. Patients enrolled in this trial had CHC with Ishak fibrosis score ≥3 on liver biopsy, a prior non-response to interferon (IFN) therapies, and no prior history of hepatic decompensation or HCC., 315 patients  met criteria of having cirrhosis at initial presentation. Most patients were overweight but not obese  and 14% (N = 147) had diabetes. During the study period, 485 patients (48.6%) were treated for HCV with 197 of these patients (41.5%) achieving SVR 12.The baseline characteristics of patients in the UMHS cohort are displayed in  Comparative incidence of outcomes among the HALT-C cohort are provided in S2 Table for reference. Patients who had fibrosis progression did not appear to have specific distinguishing characteristics compared to those who did not have fibrosis progression.In total, 140 patients in the UMHS cohort had at least 2 liver biopsies and an initial biopsy with Ishak fibrosis score <5 and were thus eligible to be assessed for the fibrosis progression outcome. At baseline biopsy, 90 patients (64%) had Ishak fibrosis stage 0–2 and 50 (36%) had Ishak fibrosis stage 3–4. The median duration between the biopsies was 3.9 years (IQR 2.1–5.7). Forty-eight (34%) patients had a ≥2-point increase in their Ishak fibrosis score over a median of 4.9 years (IQR 3.2–7.6). The baseline characteristics of patients who did and those that did not develop fibrosis progression or one of the composite liver-related clinical outcomes within the UMHS cohort are shown in S1 Fig). Among the patients with a clinical outcome, the initial event was hepatic decompensation in 164 patients (72%) and HCC in 62 patients (28%). In total, 84 patients (8.3%) were diagnosed to have HCC after a median follow-up of 6.8 years (IQR 4.1–10.7), and 184 patients (18%) developed hepatic decompensation after a median follow-up of 4.3 years (IQR 2.0–6.8). Forty-one patients (4.1%) underwent LT after a median follow-up of 5.3 years (IQR 4.3–7.3). One hundred patients (9.9%) died of which 72 developed a preceding liver-related clinical outcome. 874 (86.8%) patients were alive without LT (Table 2). The 3-, 5-, and 7-year rates of overall survival were 99.8%, 98.3% and 96%, respectively; and the corresponding rates of transplant-free survival were 99.1%, 97.1%, and 93.9%, respectively. Patients who developed a clinical outcome were older, more likely to have genotype 3 infection, cirrhosis at baseline, prior HCV treatment, were less likely to undergo treatment over follow-up and to achieve SVR. Patients with a clinical outcome also had more pronounced metabolic disease with a higher baseline BMI and higher prevalence of diabetes.A total of 226 patients (22%) in the UMHS cohort developed one of the composite clinical outcomes. The median time to clinical outcome was 4.4 years (IQR 2.3–7.9) (The model AUROCs for 1-year risk prediction was 0.62 (95% CI 0.50–0.75) among patients with complete data and 0.66 (95% CI 0.57–0.75) when imputed for patients with missing data. Given the overall small number of patients available to assess this outcome, we did not perform additional analyses to further characterize model performance for this outcome.Fig 2A. The AUROCs for models predicting composite liver-related clinical outcome at 1 year was 0.78 (95%CI 0.73–0.83) and at 3 years was 0.76 (95%CI 0.69–0.81). The variable importance graph for the model predicting composite clinical outcomes in the UMHS cohort is shown in Fig 2B. The most important independent variables for predicting composite liver-related clinical outcomes were as follows: mean APRI, baseline mean and maximum platelet count, and mean albumin. The analysis performed including patients with missing data for the predictors in the UMHS cohort yielded similar results . The proportion of patients correctly classified as high vs. low risk and the associated Brier score in our external cohort is displayed in  For clinical outcomes, the 1 and 3-year risk prediction models had a sensitivity of 80% and 69%, a specificity of 62% and 65% and a negative predictive value (NPV) of 93% and 92% respectively.Within the UMHS cohort, 31 patients (3%) developed a clinical outcome during the first year of follow-up and 80 patients (7.9%) developed a clinical outcome during the first 3 years of follow-up, and were excluded from prediction of 1- and 3-year clinical outcomes, respectively. We performed the primary analysis on the 642 and 595 patients who did not have any missing data for any of the predictor variables for 1 and 3-year risk predictions respectively. The AUROC results for the prediction model to differentiate high risk patients  from low risk patients  in the UMHS cohort is displayed in S3 Table). We also subdivided the overall cohort based on the stage of liver disease at the time of presentation to assess the effect of cirrhosis on model performance . The AUROC for 1 and 3-year risk of composite liver-related clinical outcomes among patients with cirrhosis at baseline (N = 315) was 0.70 (95%CI 0.62–0.78) and 0.69 (95% CI 0.60–0.78), and was 0.75 (95% CI 0.66–0.84) and 0.71 (95% CI 0.61–0.80) among patients without cirrhosis at baseline (N = 692).In order to assess the effect of SVR on developing clinical outcomes, we performed additional analyses. 197 patients (19.5%) achieved SVR during follow-up. These patients were younger (median age 48.6 vs 49.6), and more likely to be Caucasian (87.9% vs 78.9%) and males (68.5% vs 58.9%). A higher proportion of patients who achieved SVR had genotype 2 infection (17.1% vs 7.1%) and were treatment naïve (85.8% vs 69.9%) without cirrhosis (74.7% vs 67.3%). Among the patients who achieved SVR during follow-up, only 7 (3.5%) developed one of the composite clinical outcomes compared to 27% in those who were not treated or did not achieve SVR. Among these 7 patients with outcomes, five had baseline cirrhosis. Five patients developed HCC and two had hepatic decompensation. In one of the 7 cases, the clinical outcome occurred prior to achieving SVR. We performed a separate subgroup analysis to assess the model performance for the composite clinical outcome among those who did versus those who did not achieve SVR. The AUROC for the composite clinical outcome model among those who achieved SVR was 0.96 (0.89–1.0) and 0.94 (0.84–1.0) for 1 and 3-year risk prediction respectively. Among patients who did not achieve SVR, it was 0.77 (0.72–0.82) and 0.74 (0.68–0.80) for 1 and 3-year risk prediction respectively  and 0.80 (95% CI 0.74–0.86), respectively in the UMHS cohort . These models also retained their performance accuracy when using the entire validation cohort including patients with missing data for the predictors. A summary of model performances in the original HALT-C cohort and our external UMHS cohort is provided in S4 Table for reference.The model performance for predicting risk of HCC alone at 1 and 3 years was less robust with AUROCs of 0.70 (95% CI 0.63–0.77) and 0.65 (95% CI 0.56–0.73), respectively in the UMHS cohort Despite revolutionaly treatment advances, CHC remains a significant public health problem due to the global disease burden and the deficiencies in diagnosis and access to care and curative treatment. Given the nonlinear progression of CHC, clinical risk prediction for both short and intermediate term adverse outcomes is important if treatment delays are encountered. Obtaining accurate assessments of risk for disease progression and complications among patients who achieve SVR is also highly relevant to current clinical practice. Herein we demonstrate that highly accurate predictions for risk of adverse clinical outcomes can be made using only data obtained in routine clinical practice and across patients with diverse fibrosis stages, prior treatment exposures and response, HCV genotypes, demographics, and metabolic risk factors.We previously constructed longitudinal models with high degree of accuracy in assessing risk of fibrosis progression and adverse clinical outcomes using the HALT-C database. The performance of our fibrosis progression models was less robust in the external cohort largely due to the small numbers of patients eligible for analysis as a result of the infrequency of serial liver biopsies in clinical practice. This suboptimal performance highlights the difficulties in assessing risk for earlier outcomes such as incremental increases in fibrosis stage among patients with early stage disease. In order to assess a larger number of patients at risk for fibrosis progression but who were lacking serial biopsies, future studies would benefit from incorporating non-invasive asessment of fibrosis that are now commonly used in clinical practice, e.g. liver elastography.Our ability to accurately risk stratify patients for clinical outcomes was retained among this much more heterogeneous cohort however. Our short (1 year) and intermediate (3 year) term prediction models had robust AUROCs (0.78 and 0.76 respectively) with NPVs of 92–93%. This remained true independent of baseline cirrhosis. Interestingly, the model performance was better among patients without cirrhosis versus with cirrhosis, though this is likely is a reflection of the smaller number of patients with cirrhosis at baseline. We also demonstrated that our models remained accurate irrespective of SVR status, and in fact were more accurate among patients who achieved SVR. If validated among larger populations of patients who achieved SVR, application of these types of risk stratification models in clinical practice can help tailor monitoring post-SVR in this growing subgroup of patients. Notably, patients who developed a composite clinical outcome in our external cohort had a higher proportion of HCV genotype 3 infection and a higher prevalence of metabolic disease (higher BMI and more frequent diabetes)., 23, 24 Accurate risk assessments for clinical outcomes across a heterogeneous patient population represent the major strength of our study. The model construction based on only data routinely collected in clinical practice also facilitates application of our models into clinical practice. Several limitations are to be noted including the lack of inclusion of patients with HIV or HBV co-infection and patients with less than 3 years of follow-up. Additionally, while this external cohort was more diverse than the HALT-C cohort, it continued to have a Caucasian male predominance and mainly comprised of genotype 1 infection. Our ability to predict risk of developing HCC alone remains suboptimal and may be due to the fact that variables reflecting severity of liver disease are insufficient to predict risk of HCC. This limitation reflects the ongoing need for further investigation into the pathophysiologic mechanisms driving onconeogenesis in patients with CHC, particularly as this risk persists among patients with cirrhosis despite the achievement of SVR.In conclusion, we have successfully externally validated models for short and intermediate term risk of adverse clinical outcomes for patients with CHC among a diverse cohort of patients regardless of cirrhosis status and in those who did or did not achieve SVR. We found that patients with genotype 3 infection and those with metabolic co-morbidities had higher risk of clinical outcomes emphasizing the importance of development of effective DAA regimens for genotype 3 and prevention and reversal of metabolic abnormalities. Our models could also be applied to predict risk of clinical outcomes among patients with baseline cirrhosis who subsequently achieved SVR although the accuracy of our models in predicting HCC was low. From a health services standpoint, this statistical and clinical research approach can be applied more broadly to other forms of chronic disease in which risk stratification for adverse outcomes would be similarly germane.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.


Qatar is one of the wealthiest and fastest growing economies in the world, experiencing a rapid increase in human and pet populations. Given the paucity of data on prophylactic measures against endo- and ectoparasites of pets in Qatar, as well as on the owners’ awareness of zoonotic diseases, a questionnaire was conducted.From July to November 2017, 150 multiple-choice questionnaires were administered to dog and/or cat owners who attended two veterinary clinics in Doha.Only 54% (81/150) owners were aware of transmittable diseases between animals and humans. “Zoonosis/zoonotic disease(s)” was unknown for 88% (132/150) of the respondents and almost a quarter had no idea of transmission pathways associated with parasitic diseases. Thirteen owners (8.7%) reported to have suffered from zoonotic diseases  and 24.7% had dewormed themselves. Approximately 83% had their pets yearly vaccinated and 51% identified endo- and ectoparasites on their pets. Only 10% had their animal faeces tested for intestinal parasites as requested by a veterinarian. As for internal parasite control, only 19.3% dewormed their pets with the recommended treatment regimen (minimum quarterly); 52.7% (79/150) dewormed every 4 months to 1 year; 10% (15/150) without periodicity and 8% (12/150) had never done it. For external parasite control, only 16% (24/150) treated their pets with ectoparasiticides on a monthly basis; 44.7% (67/150) every 2 months to 1 year; 6.7% (10/150) without periodicity and 24.7% (37/150) had never done it. Approximately two thirds (63.3%) of pets were allowed to sleep in the owner’s bed and 60% to lick their owner’s face. Almost all pets were fed with dry/canned food, but 4.7% were fed with raw meat. Approximately 79.5% of dog owners collect their pet’s faeces from public areas.These results highlight the need to raise pet owners’ awareness towards prophylactic measures to minimize the potential impact of zoonotic diseases on the health of both animals and humans in Qatar.The online version of this article (10.1186/s13071-018-2720-0) contains supplementary material, which is available to authorized users. Qatar is one of the fastest and wealthiest growing economies in the world, with a rapid demographic development and a consequent increase in the animal populations. The number of dogs and cats kept as pets has also increased, as well as the number of animals that have been imported and exported from all over the world , 2.Changing demographics and concomitant human behaviour tend to favour the emergence and spread of zoonoses . In the Little information is currently available regarding prophylactic measures against parasites and vaccination programs in pets in Qatar. Similarly, limited data are accessible on the degree of pet owners’ awareness regarding zoonotic diseases. Therefore, a questionnaire was conducted to several clients in veterinary clinics of Doha, the capital and most populated city of Qatar.n = 150) who attended two veterinary medical centres located in the residential centre of Doha. Thirty questionnaires had been pre-tested to assess the suitability of different survey formats and questions (written and multiple-choice answers). The final format was a multiple-choice based interview that took approximately 6–10 min to complete  was collected, as well as on the animal species (dog/cat), age, breed, number of animals in the household, pet’s origin (shelters or pet shops/“souks”/markets or imported), feeding habits, pet’s indoor/outdoor activity, number of visits to the veterinarian and reasons for appointments, frequency of vaccination and regularity of endo- and ectoparasites prevention. Other questions included the owner’s knowledge regarding potential zoonotic diseases, i.e. if they had ever suffered from a zoonotic disease; if they were aware of the terms “zoonosis/zoonotic disease(s)”; if they had ever been treated against intestinal parasites; and their perception of potential pathways/vehicles associated with diseases transmission between people and pets.Deworming schedules and protocol guidelines from the European Scientific Counsel Companion Animal Parasites (ESCCAP) and from the Tropical Council for Companion Animal Parasites (TroCCAP) were considered to determine the most appropriate number of ecto- and endoparasiticide treatment administrations: at least quarterly for worm control  and monthly for ectoparasite control –8.P-value < 0.05 regarded as statistically significant. Analyses were performed with SPSS®21 for Windows.The Chi-square test and Fisher’s exact test (FET) were used to compare proportions, with a Overall, out of the total respondents, 51.3% (77/150) were sole cat owners, 30.7% (46/150) sole dog owners and 18% (27/150) were both cat and dog owners. Concerning the nationality of interviewees, they came from 31 origin countries, with British as the most representative nationality with 24% (36/150), followed by 16% (24/150) Qataris and 8% (12/150) Indians. The average age of the respondents was 37.5 years old (standard deviation: 10.9), with females representing 62.7% (94/150) of the owners questioned.The most popular pet in Qatar was found to be the cat, with 69.3% (104/150) of the respondents having at least one cat and 51.3% of owners having only cats as their companion animals. Cat households had an average of 2.4 cats, ranging from 1 to 11. Out of the 251 cats of this study, the Domestic Shorthair was the most popular breed (166/251), followed by Persian (34/251). Breeds like Scottish Fold, British Shorthair and Longhair, Turkish Angora, Himalayan and Sphynx were also reported.Dog owners represented 48.7% of the respondents, with 73/150 as having at least one dog. Around 30.1% (46/150) of the households had only dogs as a companion animal. Dog households had an average of 1.8 dogs, ranging from 1 to 7. Out of the 127 dogs of this study, Saluki and mixed-Saluki represented the majority of the dog breeds (31/127), followed by unspecific breed (17/127), Labrador Retriever (9/127), Golden Retriever (7/127). Cocker Spaniel, German Shepherd, Pomeranian, Dachshund, Schnauzer and Havanese were also reported. Additionally, 18% (27/150) of the households had both cats and dogs as companion animals.Rescued animals represented 44% (66/150) of the population, as the majority of the respondents had either adopted their pets from the streets [32.7% (49/150)] or from shelters [11.3% (17/150)] in Qatar. In addition, 24% (36/150) of the owners imported their pets from foreign countries to Qatar , with the UK and Ukraine as the most common sources for these pets . Pets purchased from shops [6.7% (10/150)], markets (“souks”) [7.3% (11/150)] and breeders [1.3% (2/150)] represented 15.3% (23/150) of the pet population.The major reason why owners visit the veterinarian was for vaccinations [82% 123/150)], followed by pet sickness [38.7% (58/150)], regular health checks [24% (36/150)], pet check/ blood tests and necessary prophylaxis (vaccination/deworming) prior travel [16% (24/150)], deworming administration [13.3% (20/150)] and grooming [6% (9/150)]  had their pets on a yearly vaccination program, with 64.7% believing that the vaccination of pets protects both human and animal health, 18.7% that it protects only animals and 2% for their own protection  by only 19.3% (29/150) of the owners, 52.7% (79/150) dewormed every 4 months to 1 year, 10% (15/150) with no defined pattern of frequency and 8% (12/150) had never internally dewormed their pets . In addition, people who reported to have previously suffered from a zoonotic disease were also more aware of dermatophytosis than those not affected by a zoonotic disease .Of the 150 owners surveyed, 54% (81/150) were aware of transmittable diseases between animals and humans (Table n = 6), magazines/books (n = 6), internet (n = 4) and school (n = 4) were the most common sources of information referred. Additionally, of those 10.7% (16/150) who worked in the healthcare field , only 12 were able to give examples of diseases transmittable between animals and humans, only five had heard of “zoonosis/zoonotic disease(s)” and just four were able to define its meaning. Thirteen owners (8.7%) had suffered from zoonotic diseases, of which 10 from dermatophytosis, two from cat-scratch disease and one from an unknown tick-borne disease. In three out of these 10 infections, owners had a health profession-related illness .Veterinary practitioners , raw meat , soil  and plants  more frequently than people with non-health-related professions.When questioned about possible pathways of transmission of parasites to animals, 73 indicated animal faeces, 57 raw meat, 40 soil samples, 39 food items, 37 arthropods, 31 mother-to-child, 20 plants, 18 environmental contamination and one claw scratch. Almost a quarter of the respondents [24.7% (37/150)] had no idea of pathways of transmission Table . Health Although almost all dogs and cats were fed with dry and/or canned pet food, still 4.7% (7/150) of the owners fed their pets with raw meat. 73.3% (110/150) of the household pets were allowed to have access to their owners’ bedroom, 63.3% (95/150) to sleep in the owner’s bed and 60% (90/150) to lick the owner’s face. Of the total respondents, 61.3% (92/150) keep their animals strictly indoors, 35.3% (53/150) indoors with outdoor access and 3.3% (5/150) have them exclusively outdoors  and more than a half (52.7%) deworming every 4 months to 1 year. These results contrast with other international studies, namely from Australia, where a much higher anthelmintic administration frequency was found, with 54% of dogs being dewormed quarterly . The lowDespite the potential occurrence of zoonotic parasites previously detected in the country , 12, 13,Veterinarians should play a central role in the promotion of pet owners’ education towards zoonotic diseases and about proper treatment and prevention strategies . AdditioConsidering that the number of imported pets from foreign countries to Qatar represents at least 22% of the population in this study, treatment of all imported animals against intestinal helminths and ectoparasites upon arrival is critical to prevent introduction of non-endemic parasites. The same recommendation should be implemented on pets relocating from or travelling to foreign countries . Aside from intestinal helminths and protozoans in the stray animal population in Qatar, a screening for vector-borne diseases should be implemented as part of the routine health check of all animals being exported from Qatar, especially when they are being relocated in countries where these diseases are not endemic .Additionally, some behavioural practices reported, such as feeding their pets with raw meat or the close physical contact between owners and pets, show a lack of knowledge regarding animal and public health issues. In the households assessed in Doha, 73.3% of the pets were allowed to have access to their owners’ bedroom, 63.3% to sleep in the owner’s bed and in 60% to lick the owner’s face. These results are similar to those found by Matos et al. , who repRegarding the collection of dog faeces, almost 79.5% of the owners claimed to collect them. This means that approximately one fifth 20.5%) of the owners were not performing it, which is considerably lower than the 37% reported in Portugal [.5% of thThis study identified several risk factors for the transmission of parasitic zoonoses associated with pet ownership in Qatar. Other relevant risk factors such as the presence of children or immunocompromised members in the family, slaughter practices, drinking water sources and education level  should also be included in future analyses. It might be useful to extend this study to owners living in rural environments and compare the results, practices and risk factors with those living in the city center. Our results highlight the need to raise pet owners’ awareness toward transmittable diseases and effective prophylactic measures to minimize the risk of zoonotic diseases in Qatar.Additional file 1:Figure S1. Multiple-choice questionnaire administered to dog and/or cat owners who attended the veterinary medical centres surveyed in the residential centre of Doha. (DOCX 121 kb)


We report patient outcomes after antiretroviral therapy (ART) initiation in a network of HIV facilities in Haiti, including temporal trends and differences across clinics, during the expansion of HIV services in the country.We assessed outcomes at 12 months after ART initiation (baseline) using routinely collected data on adults (≥15 years) in 11 HIV facilities from July 2007-December 2013. Outcomes include death , lost to follow-up (LTF) defined as no visit > 365 days from ART initiation, and retention defined as being alive and attending care ≥ 365 days from ART initiation. Outcomes were compared across calendar year of ART initiation and across facilities. Risk factors for death and LTF were assessed using Cox proportional hazards and competing risk regression models.Cumulatively, 9,718 adults initiated ART with median age 37 years (IQR 30–46). Median CD4 count was 254 cells/uL (IQR 139–350). Twelve months after ART initiation, 4.4% (95% CI 4.0–4.8) of patients died, 21.7% (95% CI 20.9–22.6) were LTF, and 73.9% (95% CI 73.0–74.8) were retained in care. Twelve-month mortality decreased from 13.8% among adults who started ART in 2007 to 4.4% in 2013 (p<0.001). Twelve-month LTF after ART start was 29.2% in 2007, 18.7% in 2008, and increased to 30.1% in 2013 (p<0.001). Overall, twelve-month retention after ART start did not change over time but varied widely across facilities from 61.1% to 86.5%.Expansion of HIV services across Haiti has been successful with increasing numbers of patients initiating ART and decreasing twelve-month mortality rates. However, overall retention has not improved, despite differences across facilities, suggesting additional strategies to improve engagement in care are needed. Over the past decade, the scale-up of HIV services, particularly access to antiretroviral therapy (ART), in resource-poor settings has been enormously successful with over 18 million adults initiating treatment –9. ThougHaiti is the poorest country in the Western Hemisphere with the highest adult HIV prevalence in the region, which was 6.2% in 1993 and decreased to 1.7% in 2014 –19. An eThe objective of this analysis is to evaluate outcomes during the first twelve months after ART initiation among adults starting treatment within the GHESKIO-MSPP network from 2007 through 2013. We evaluate mortality, LTF and retention rates at 12-months after ART initiation, as well as temporal trends and differences across clinics.The study population includes adults ≥ 15 years who initiated ART in the GHESKIO-MSPP network of HIV facilities with electronic medical records (EMR) from July 1, 2007 through December 31, 2013. While a small number of network facilities provided ART as early as 2005, patient-level data was not routinely collected in the iSanté EMR system supported by the MSPP until in July 2007 , 25. AmoEligibility for ART initiation followed national and WHO guidelines and included WHO Stage IV and/or CD4 count ≤ 200 cells/uL from 2007 to 2009, and WHO stage III or IV and/or CD4 count ≤ 350 cells/uL from 2009 through 2013 , 27. Fro2. Date of ART initiation was defined as the first date that ART was dispensed during the study period, with no prior history of documented ART. WHO stage, CD4 count, weight and height measurement at time of ART were defined as the measurement closest to ART start date within a 3-month window period. A diagnosis of TB was defined as a documented TB diagnosis in the iSanté database at the date of ART initiation. Guidelines for TB diagnosis in Haiti include presence of TB symptoms, chest x-ray suggestive of TB, and positive microscopy and or culture which is consistent with other studies [Sociodemographic and clinical measurements at the time of ART initiation included sex, age, HIV testing point of entry, body weight (kilograms), height (centimeters), WHO Stage, CD4 count, tuberculosis (TB), and ART regimen. Body mass index (BMI) was calculated as kilogram/meter studies , 28. CliPatient information was documented by health care providers on national patient forms and subsequently entered by trained data clerks into the iSanté EMR. Data quality assessments were done quarterly to check for completeness and accuracy comparing paper records to data in the electronic database.Facility-level characteristics included facility type  and facility location  based on characteristics provided by MSPP, as well as clinic size (number of patients cumulative on ART during the study period).Patient outcomes are mutually exclusive and included death, lost to follow-up (LTF) and retention in care at 12 months after date of ART initiation. Death refers to all-cause mortality documented in the EMR within 365 days of ART initiation. Lost to follow-up at twelve months after ART initiation was defined as no documented death or transfer prior to 365 days and no clinic visit after 365 days from date of ART initiation. Retention at twelve months was defined as being alive and attending clinic with documented visits in the medical record greater or equal to 365 days from the date of ART initiation.De-identified data on sociodemographic and clinical variables were extracted from the EMR. The probability of mortality after ART initiation was estimated using Kaplan Meier methods, censoring patients who were lost to follow-up at the time of their last visit. The cumulative incidence of LTF after ART initiation was estimated by treating death as a competing risk as outlined by Coviello and Boggess . PatientThis analysis was approved by the institutional review boards at Weill Cornell Medicine, Centers for Disease Control, and the Ethics Board at GHESKIO.2 [A total of 9,718 adults ≥ 15 years initiated ART in 11 GHESKIO-MSPP HIV facilities across Haiti . The maj2 . A totalTwelve-month outcomes after ART initiation among all patients who initiated ART from 2007 through 2013 include the following: 4.4% (95% CI 4.0–4.8) patients died, 21.7% (95% CI 20.9–22.6) were LTF, and 73.9% (95% CI 73.0–74.8) were retained in care.From 2007 to 2013, the median age at time of ART initiation remained greater than 35 years and the majority of patients were female . Among 7The trend in the 12-month mortality rate after ART initiation decreased from 13.8% (95% CI 9.8–19.1) in 2007 to 4.4% (95% CI 3.5–5.6) in 2013 (p< 0.001) , Fig 2. The overall mortality rate in the first three months was 7.1 deaths/100 person years as compared to 2.6 deaths/100 PY from one to five years after ART initiation among patients with follow-up time greater than one year . The morAcross HIV facilities, median age differed from 35 years to 42 years (p< 0.001) . Median Mortality rates at 12-months after ART initiation ranged from 1.6% (95% CI 0.8–3.3) to 8.7% (95% CI 6.5–11.6) across clinics (p< 0.001) , Fig 2. Individual-levels factors associated with death at 12-months after ART initiation include male gender (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1–15), WHO Stage III/IV , CD4 count < 100 cells/uL  and BMI < 18.5 kg/m2  . No faciAll patients older than or equal to 25 years, as compared to 20–24 year-olds, had a decreased risk of LTF. Patients with WHO Stage III/IV disease had a 30% increased risk of LTF as compared to patients with WHO Stage I/II disease . Patients who initiated ART in HIV facilities with ≥ 1000 cumulative patients on ART during the study period, were at higher risk for LTF as compared to those as smaller clinics . Additionally, patients who initiated ART at rural or semi-urban clinics, as compared to urban clinics, were less likely to be LTF .This cohort study of 11 HIV facilities includes approximately 10,000 patients and reports outcomes during the first year after ART initiation during a period of expansion of HIV services in Haiti. From 2007 through 2013, there was a steady increase in the number of patients initiating ART in this network of HIV facilities. At 12 months after ART initiation, 4.4% of the study population died, 21.7% were lost to follow-up, and 73.9% were alive and retained in care. While there was a decreased trend in mortality rates at 12-months after ART initiation, LTF increased such that there was ultimately no improvement in retention over time. Additionally, a substantial heterogeneity in outcomes was seen across clinics and warrants further investigation to understand best practices in clinics with optimal outcomes to share with poorer performing clinics.This study’s overall mortality rate at 12 months after ART initiation of 4.4% is slightly lower than rates from other studies in low and middle-income countries and from patients treated at GHESKIO’s central HIV specialty clinic in Port-au-Prince . In a meOur finding of a decrease trend in 12-month mortality among patients initiating ART from 2007 to 2013 is similar to findings from an analysis of 12-month mortality trends across 8 clinics in South Africa, which reports mortality decreased from 8.9% in 2002 to 5.6% in 2007 , 11. IntDirect comparison of our results of LTF to other studies may be limited given differences in definitions of LTF across studies. Our rates of LTF are higher than the rate of 16.1 persons/100 PY who were lost in the first six months of treatment reported among patients who initiated ART between 1999 and 2008 in the GHESKIO HIV specialty clinic in Port-au-Prince , 33–36. Undocumented, or silent, transfers are hypothesized to be a significant problem in Haiti by local HIV providers. Unfortunately, there is no unique national identification number in Haiti to track patients across clinics in the EMR. Our study found that patients who initiated ART in urban HIV facilities were more likely to be LTF which may be due, in part, to patients transferring without documentation to clinics closer to their homes in rural areas. Currently, the MSPP is evaluating a finger-print tracking system as a unique identifier of HIV patients across sites to better understand patient transfer and migration. The fact that 30% of patients who initiated ART in this cohort never returned to the clinic also points to a subgroup of LTF patients who may be distinct from patients who disengage later during care, and additional research is needed to understand each group’s unique barriers to care. Data management is another challenge given the poor physical infrastructure of the electronic medical record system in these clinics. In an assessment of data quality of variables in the iSanté database, TB status and ART eligibility were incomplete 20–40% of the time, and discontinuation forms, which document dates of transfer, death, and LTF status were entered late .Of note, there are no significant differences in outcomes noted in the year following the historic earthquake which occurred in January 2010. Comparing outcomes among patients who initiated ART in the year prior to the earthquake in 2009 to 2010, the cumulative incidence of mortality was 5.2 (95% CI 4.1–6.6) versus 5.4 (95% CI 4.3–6.7) with overlapping confidence intervals. Lost to follow-up was also similar in 2009 at 17.8 (95%CI: 15.8–19.8) and in 2010 was 15.3 (95%CI: 13.4–17.2) with overlapping confidence intervals. This is a similar finding to previous analyses we have conducted pre- and post-earthquake reporting that the 2010 earthquake did not significantly impact outcomes of LTF or death among HIV patients .Multiple interventions are being evaluated to improve retention in care among patients who start ART in Haiti. Early work with directly observed therapy for ART using community workers has shown promising results . Fast trThe marked heterogeneity in outcomes across facilities has been reported in other multi-country cohort studies , 11, 36.A strength of this study is the inclusion of a unique set of HIV facilities in Haiti that have not previously been reported. The majority of ART outcomes in Haiti have been previously reported from the GHESKIO central clinic in Port-au-Prince, which is a specialty clinic included in the CCASAnet cohort , and a regional leader in both HIV research and service delivery , 28, 46.Despite multiple social and economic challenges that occurred in Haiti during the study period, including political instability, a catastrophic earthquake in 2010, and a devastating cholera epidemic, Haiti was able to successfully expand HIV services across the country . This stS1 Table(DOCX)Click here for additional data file.


Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information. For this cross-sectional “snapshot” analysis, 556 patients with a confirmed diagnosis of DM1 registered between May 2012 and July 2016 were included. An almost even distribution was seen between genders and a broad range of ages was present from 8 months to 78 years, with the largest proportion between 30 and 59 years. The two most frequent symptoms were fatigue and myotonia, reported by 79 and 78% of patients, respectively. The severity of myotonia correlated with the severity of fatigue as well as mobility impairment, and dysphagia occurred mostly in patients also reporting myotonia. Men reported significantly more frequent severe myotonia, whereas severe fatigue was more frequently reported by women. Cardiac abnormalities were diagnosed in 48% of patients and more than one-third of them needed a cardiac implant. Fifteen percent of patients used a non-invasive ventilation and cataracts were removed in 26% of patients, 65% of which before the age of 50 years. The registry’s primary aim was to facilitate and accelerate clinical research. However, these data also allow us to formulate questions for hypothesis-driven research that may lead to improvements in care and treatment.The online version of this article (doi:10.1007/s00415-017-8483-2) contains supplementary material, which is available to authorized users. In most populations myotonic dystrophy is the most common muscular dystrophy. With an estimated prevalence of 10 per 100,000 people affected in European populations , we estidystrophia myotonica-protein kinase (DMPK) gene on chromosome 19 [DM1 is the result of a triplet CTG repeat expansion in the 3′-untranslated region of the osome 19 . The divosome 19 , 13. Theosome 19 –16 and hosome 19 –21.www.treat-nmd.eu). The registry is coordinated from the John Walton Muscular Dystrophy Research Centre at Newcastle University and collects clinical and genetic information about both DM1 and myotonic dystrophy type 2 (DM2). A total of 610 patients enrolled by July 2016, here we report the demographic and clinical findings for the 556 symptomatic DM1 patients registered.The UK Myotonic Dystrophy Patient Registry was established in May 2012 with support from the Muscular Dystrophy UK (MDUK) and the Myotonic Dystrophy Support Group (MDSG), assisted by the TREAT-NMD Alliance  who, using a separate online account, enters clinical and genetic details. This includes professionals from secondary healthcare only and does not include general practitioners (GPs). This bespoke system allows the healthcare professional to amend any inconsistencies in the patient data, while providing the necessary clinical and genetic details. This has been tested through a compliance check performed on a random sample of 26 patient records  which showed a high level of consistency between patient and clinician data across three of the patient-reported symptoms .http://www.dm-registry.org/uk).Participants are encouraged to update details annually allowing for the collection of longitudinal data. Informed consent is provided online and allows for future contact to be made, data provided to be used in research, and for the additional data to be entered by a nominated professional. The registry has received full ethical (Newcastle and North Tyneside 1 11/NE/0179) approvals for conducting these activities in the UK. The operation and maintenance of the registry is carried out by a part-time curator at an annual budget of approximately £15,000. It is governed by a steering committee comprising multiple stakeholder groups who adhere to Terms of Reference and Standard Operating Procedures  conρ. Chi-square test and if appropriate Fisher’s exact test were applied in categorical variables to determine statistical significance. p values less than 0.05 were considered to be statistically significant.Statistics have been carried out using IBM SPSS statistics 22. Correlation between two ordinal variables (e.g. severity of symptoms) has been calculated using Spearman’s A total of 610 patients registered in the UK Myotonic Dystrophy Patient Registry between May 2012 and July 2016. A steady increase in registrants has been observed with the largest growth in numbers seen when the registry launched. On average 13 patients registered each month. Sixty-seven healthcare professionals  have engaged and agreed to contribute data to the registry  of patients although the detail of the family relationship between affected persons was not collected. Caucasian ethnic origin was reported by 97.3% 532/547) of registrants, Asian by 0.009% (5/547), Black African by 0.002% (1/547) and mixed by 0.02% (9/547). A wide geographical distribution was seen with some clustering around the large neuromuscular centres in Newcastle, Oxford, and London , with relatively more patients having mild fatigue among the patients with mild myotonia, and relatively more patients having severe fatigue among the patients with severe myotonia . Dysphagia occurred significantly more frequently in patients with myotonia  compared to patients without myotonia .The most commonly reported symptoms in the registry were fatigue/daytime sleepiness and myotonia, reported by 79.1 and 77.9% of patients, respectively Table . These sA treatment with modafinil was given in 18.5% 80/432) of patients with fatigue and 7.4% (32/432) used non-invasive ventilation. Medication to help manage myotonia was reported by 6.4% (27/422) of patients with myotonia, with the most common medication mexiletine reported in 40.7% (11/27). Dysphagia was reported in 48.2% of patients , were ambulant not using any assistive device to walk, 31.8% (174/548) required some assistance, and 3.3% (18/548) were non-ambulant. Of the patients needing some assistance, wheelchair use was reported by 56% (94/168) of patients, including 95.7% (90/94) of them using a wheelchair part-time and 4.3% (4/94) using a wheelchair most of the time. The age at which wheelchair use began ranged from less than 1 to 72.4 years . Among the wheelchair users 22.8% (32/129) started before the age of 10 years and 56.6% (73/129) started to use a wheelchair between 30 and 59 years.A routine electrocardiogram was reported for 33.8% (188/556) and a heart condition (arrhythmia or conduction block) was reported in 48.2% of patients (Table p = 0.001). Seventeen percent (6/35) of patients with ventilation were under the age of 30 years and there was no one registered with invasive ventilation. The age at which ventilation began was not recorded. The results of pulmonary function testing were reported in 25.9% (144/556) of patients, with 52.8% (76/144) being normal ), 14.6% (21/144) showed moderate (60–69% FVC), 13.9% (20/144) moderately severe (50–59% FVC) and 18.8% (27/144) severe (<50% FVC) restriction. Of those with severe restriction, 22.2% (6/27) of patients reported using non-invasive ventilation, 80% (20/25) reported fatigue and 51.9% (14/27) used a wheelchair at least part time. Of the patients with an FVC of greater than 70%, 5.3% (4/76) were using a wheelchair part time compared to 42.4% (28/66) of those with an FVC below 70%.Regular and ongoing non-invasive ventilation was needed in 14.9% of patients Table , 52.9% (Information about cataract surgery was available for 40.1% 223/556) of patients registered, of which 26% had cataracts removed (Table 23/556 ofThe age of genetic diagnosis was available for 33.8% (188/556) of patients and ranged from birth to 72 years . The diagnosis of a large proportion of patients, 65.4% (123/188), took place between 20 and 49 years. There was a notable age gap between the age of symptom onset and the age of genetic diagnosis; 14.9% (20/134) participants received a genetic diagnosis within 12 months of symptoms onset and 13.4% (18/134) had the genetic diagnosis before the age of onset. However, the mean period from onset of symptoms to genetic diagnosis was 9.1 years (SD ±11.1), for those with symptoms before diagnosis the delay was 11.1 (SD ±10.4) years.The CTG repeat length reported from standard diagnostic testing was only available for 11.3% (63/556) of patients registered and ranged from 21.7 to 867 CTG trinucleotide repeats . Information about age at onset was given for 81% (51/63) of those with a repeat number available, 3.9% (2/51) of which were categorised as congenital onset, 5.9% (3/51) as infantile, 35.3% (18/51) as juvenile, 31.4% (16/51) as adult, and 23.5% (12/51) as late adult onset. The two patients reporting congenital onset had a reported CTG repeat number of 450 and 700, those with infantile onset had repeats between 700 and 833, juvenile onset patients had 129–867 repeats, adult onset 67–700, and repeat numbers of patients with a late adult onset varied from 70 to 700. The mean age at which the genetic testing was performed was 13.5 years for patients with congenital onset, 28.1 years for infantile onset patients, 27.9 years for patients with juvenile onset, 37.3 years for adult onset, and 52.2 years for patients with late adult onset.The severity of symptoms  was not correlated to the repeat size at the time of diagnostic testing.p = 0.006) and men had significantly higher occurrence of severe myotonia (p = 0.021). Fatigue occurred almost as frequently in men as in women (Table p = 0.028). Although not statistically significant, more male patients reported dysphagia compared to female DM1 patients (p = 0.21). There were more male patients with mobility impairments (p = 0.84), wheelchair use (p = 0.74), cardiac abnormalities (p = 0.42), and the need of non-invasive ventilation (p = 0.56), whereas more women had cataracts removed (p = 0.24), but these differences were not statistically significant.Myotonia was reported significantly more frequently by male patients compared to females  across the country has helped establish a virtual network of medical professionals with an interest in myotonic dystrophy and research into the condition . The regThere are limitations to a patient initiated registry and the design of this registry does include an element of self-selection, therefore we cannot assume this cohort is fully representative of the entire DM1 population in the UK. The nature of the registry means that inclusion is biased towards those that are able, willing, and interested to participate in clinical research. It may be speculated that this snapshot represents the less severe and more engaged population of the DM1 population in the UK. However, it could be argued that more severely affected patients may engage more with research as there is a greater impact on their daily lives. The reliability of the patient-reported symptoms such as myotonia could also be questioned as these terms may not be accurately understood by patients, this may be a specific concern in DM1 considering the cognitive impairment present in many. However, a limited compliance check across three centres showed the reliability of patient-reported data to be very promising, validating the move towards an increase in self-reported outcomes. Furthermore, evidence suggests that patients gain additional benefit from this level of engagement .Clinical and genetic information is not available for some patients; this is due to some delays in obtaining local R&D approvals and the burden on the professional’s time. Without full integration into the healthcare system or provision of resources at a larger scale it may not be possible to capture complete genetic and clinical information on all patients.To improve the completeness of the data a larger proportion of the data items could be completed by the patient themselves, particularly relating to the age at onset and questions regarding medications and ventilation. Having more information about how many patients have tried a treatment but failed to tolerate it could help to improve current best practice and warrant future investigation.The registry has already helped to formulate hypothesis for future studies which may lead to better understanding of the condition. For example, the data presented support a recent study indicating gender differences in DM1 . SimilarThe most prevalent symptom described in the registry is fatigue and excessive daytime sleepiness, known to also be one of the most disabling leading to disability, unemployment, family breakdown, and reduced quality of life , 27. CliA correlation between dysphagia and myotonia has been observed in the registry data, with dysphagia occurring more frequently in patients who also report myotonia. This positive correlation is also seen between myotonia and mobility impairment. This is contradictory to the authors’ clinical impression that dysphagia is associated with muscle weakness and is negatively correlated with myotonia. Further clinical investigation may allow us to understand these findings as they could impact care and treatment.The data presented suggest that there is a significant delay between symptom onset and genetic diagnosis . This haOur data regarding diagnosis could be improved with better characterisation of age of onset and inclusion of presenting symptom. This could help better understand if certain symptoms such as bowel dysfunction (information about which is not currently collected), cataracts, or excessive daytime sleepiness may not be picked up as quickly as muscle weakness or grip myotonia as suggested by previous studies , 33. As The registry allows self-reported outcomes to be collected from a large cohort of patients with direct and ongoing access. The results shown here may inform the design of future academic studies into the pathophysiology of the condition and provide relevant information for clinical trials. The collection of longitudinal data over time will provide an additional resource when assessing the progression of the condition.The common TREAT-NMD dataset is shared by at least 19 registries across 17 different countries . Ideally, all registries would be linked centrally by this common dataset allowing data to be shared across the research community. The TREAT-NMD Alliance has successfully established a global network of national registries for Duchenne muscular dystrophy and spinal muscular atrophy , 35 and http://www.rd-connect.eu) [Increased harmonisation and collaboration not only between registries, but also across resources could enable communication between different health care systems in a sensitive and secure manner. This kind of collaboration and data sharing is key to understanding the natural history of these complex and rare diseases and there are number of initiatives in Europe currently looking at ways to achieve this, for example RD-Connect (nect.eu) , 36.The UK Myotonic Dystrophy Patient Registry is an example of a novel, online-based, cost-effective, and patient-driven registry. Its success can be measured by its continuous growth and utilisation. Although primarily designed to accelerate and facilitate trial recruitment and planning the registry has also provided and interesting and important data characterising the DM1 patient community in the UK.Supplementary material 1 (DOC 2832 kb)Supplementary material 2 (DOC 2848 kb)Supplementary material 3 (PDF 103 kb)Below is the link to the electronic supplementary material.


To investigate the clinical characteristics and prognosis of primary malignant melanoma of the uterine cervix.The median age of the patients was 61.2 years . The median overall survival of the patients at stage I, II and III were 39.2 months, 47.8 months and 9.0 months (P=0.574) and the 2-year overall survival for each stage were 80.0%, 50.0% and 0.0% respectively. Twelve (85.7%) patients developed recurrence and eleven patients (78.6%) died. Ten patients received surgery and four patients were treated with chemotherapy and/or radiotherapy. Immunotherapy was administrated to two patients after surgery. The mean survival time of patients with surgery and without surgery were 47.9 vs.7.75 months (P=0.047). Patients received radical hysterectomy had longer survival than patients underwent total hysterectomy .Clinical data from 14 patients with primary malignant melanoma of the cervix between January 1981 and December 2014 were reviewed.Patients with primary malignant melanoma of the cervix have a poor prognosis. Radical hysterectomy and pelvic lymphnode dissection may offer better prognosis for stage I and II patients. Malignant melanoma (MM) is a rare malignant neoplasm of the skin and mucous membranes and accounts for about 1% of all cancers . 5% femaCurrent treatment for mucosal melanoma is primarily based on experience from cutaneous mela-noma. Optimal management of cervical MM have not achieved consensus due to scarcity –7. To ouHere we reported 14 cases of primary MM of cervix and reviewed the literature. Our aim was to explore the best treatment strategy for this rare disease.Fourteen patients with primary MM of cervix were included in our study. The mean age was 61.2 years. All patients presented with vaginal bleeding. The maximum tumor diameter ranged from 2.0cm to 7.0cm. The tumor was exclusively or primarily located in cervix regardless of vaginal involvement. There was no sign of vulval lesion. Patients` final stages were 5 stage I, 6 stage II and 3 stage III. Main clinicopathologic characteristics are summarized in Table The detailed treatment approaches are presented in Table Three patients only received chemotherapy and radiotherapy due to advanced stage. Patient No.9had surgical contraindication (arrhythmia)received chemotherapy.The median follow-up time was 22.5 months 4.0 to 193.0 months). Twelve (85.7%) patients developed recurrences or presented persistent disease. Eleven (78.6%) died of the disease. All the four patients dismissed surgery had persistent disease. Time interval for recurrence from first treatment varied between 2.0 to 24.0 months post  remained without evidence of disease; one patient (No. 8) was alive with disease at the time of last follow-up. Two patients 14.3%, 2/14) lived for more than five years and seven  survived over two years . The patients who did not receive surgery had persistent disease and died at 4, 5, 10 and 12 months.Of the 10 patients who underwent surgery, eight patients developed recurrences and 7 patents died of it. The mean survival time of four patients received TH was 19.5months (9 to 28), and was 66.8 months(20 to 193) for six patients received RH (P=0.016). All patients (3) were alive had radical hysterectomy and pelvic lymph node dissection.The median OS of the 7 patients underwent surgery and adjuvant therapy was 28.0 months, and six  of them had recurrence. All three patients without adjuvant therapy experienced recurrence. For them, two died at 25.0 and 20.0 mouths, and one was alive for 51.0 months with residual tumor at the last contact.The mean OS of the patients at stage I, stage II and stage III were 39.2 months, 47.8 months and 9.0 months respectively(P=0.574). The 2-year survival of each stage were 80.0% (4/5), 50.0% (3/6) and 0.0% (0/3) respectively.Primary malignant melanomas of cervix is an extremely rare disease which origin from the cervical melanocytic cells . DiagnosIn early stage, the primary MM of the cervix localized to the cervical mucosa, and spreads to vaginal fornix, uterosacral ligaments, vulva and pelvic wall at advanced stages , 12. LymCurrent staging system for skin MM is based on tumor thickness and the status of regional lymph nodes ;by contrWhile little consensus has been achieved about the best management of cervical MM, surgery remains the major therapeutic method , 11, 17.Whether dissection of clinically negative regional lymph-nodes is still controversial. Jones et al found that 30% of patients with clinically normal lymph-nodes at presentation contained microscopic melanoma and suggested regional lymph node dissection . By contGreat attempts have been made to evaluate the potential benefits of adjuvant chemotherapy. There is no chemotherapeutic regimen which has valid effect on reducing or delaying the recurrence. Most authors used the chemotherapy for MM of the skin melanoma , 5. DacaLpilimumab, a monoclonal antibody directed to the immune checkpoint receptor termed “cytotoxic T lymphocyte antgen-4 (CTLA-4)”, received FDA approval for treatment of metastatic melanoma in March 2011. The approval was based on two randomized phase III trials in which Lpilimumab improved the survival of metastatic melanoma , 25. RecMM is considered a radio-resistant tumor. RT applied as adjuvant, preoperative and palliative treatment in some case reports . AdjuvanTumor stage is the main prognostic factor of this rare disease , 3. OnlyThe largest case review of primary MM showed the mean and median overall survival were 22.9 and 12 months(range 0.1–168 months)respectively. Mean/median OS stratified by stage were 31.5/20 months (ranges 1–156) for stage I, 22.8 /10.5 (ranges 0–168) for stage II, 14.5 /11 (ranges 6–34) for stage III, and 5.75/5 months (range 1–12) for stage IV  in a perIn conclusion, patients with primary malignant melanoma of the cervix have a poor prognosis and radical hysterectomy may offer better outcome for STAGE I1 OR II2 patients.We reviewed the records of all patients who were presented to the Cancer Hospital of Chinese Academy of Medical Science with a diagnosis of primary malignant melanoma of the cervix from January 1, 1981 to December 31, 2014. Surgical and pathological reports were reviewed. Gynecologic pathologists confirmed all the histopathologic diagnoses. Demographic and clinical information, including age at the time of diagnosis, presenting symptoms, tumor characteristics, treatment and follow-up were obtained from medical records.Treatment modalities were classified as three categories: surgery, chemotherapy and radiation therapy. Overall survival was the primary end point result.All data were analyzed by SPSS . OS was calculated from the date of initial treatment to the date of last follow-up by Kaplan-Meier method. The threshold for significance was set at P<0.05.


The further researches on physiological traits showed a rapid decrease in the green leaf area index (GLAI) and chlorophyll content and a remarkable increase in malondialdehyde content in high plant density (HPD) population than did the low plant density (LPD) population, which indicated the rapid leaf senescence. However, HPD had higher values in terms of pod area index (PAI), pod photosynthesis, and radiation use efficiency (RUE) after peak anthesis. A significantly higher level of dry matter accumulation and nitrogen utilization efficiency were observed, which resulted in higher yield. HPD resulted in a rapid decrease in root morphological parameters . These results suggested that increasing the plant density within a certain range was a promising option for high seed yield in winter rapeseed in China.In this study, the yield and yield components were studied using a conventional variety Zhongshuang 11 (ZS 11) and a hybrid variety Zhongyouza 12 (ZYZ 12) at varying plant densities. The increase in plant density led to an initial increase in seed yield and pod numbers per unit area, followed by a decrease. The optimal plant density was 58.5 × 10 Brassica napus L.) is widely cultivated along the Yangtze River in China, which represents approximately 30% of the total oilseed production worldwide and 89% of the oilseed yield in China [Oilseed rape is one of the most important sources of edible oil in the human diet. In recent years, the seed yield has lagged behind the increasing demands driven by population growth. Therefore, the yields of rapeseed crops must be significantly increased . Winter in China . Increas−2 before winter and 60–80 plants m−2 at the beginning of spring [−2 [Plant density is an important factor affecting seed yield and yield components of oilseed rape , 4 and cf spring . Howeverring [−2 , 11. In ring [−2 . TherefoPrevious studies have demonstrated that photosynthate supply plays an important role in pod and seed development , 13–15. In winter oilseed rape, the leaves are the main photosynthetic source before anthesis, whereas the lower part of the plant canopy becomes part of the source after anthesis, and during pod development, the photosynthetic rate from green pods during seed filling contributes to approximately 2/3 of the total seed weight . There hThe field trials were conducted from 2010 to 2014 at Yangluo Experimental Station of the Oil Crops Research Institute in Wuhan, Hubei, China , which is located approximately in the center of the Yangtze River basin. This area is characterized by yellow-brown soil in the experimental field. The surface soil (0–30 cm) was sampled at the beginning of each growing season. The soil samples were air dried, ground, and analyzed for pH value, dissolved organic carbon (DOC), total nitrogen, alkaline digested N, available phosphorus, available potassium, and available boron contents . The soi4, 37.5 × 104, 48.0 × 104, 58.5 × 104, and 69.0 × 104 plants ha−1), and the subplots comprised two varieties. Each subplot was 2 × 10 m, with rows approximately 30–35 cm apart (three rows per meter). The plants were finalized by hand when the seedlings had fully developed 4-5 true leaves, and the spaces between seedlings ranged from 4 to 11 cm to achieve different planting densities. Each plot was fertilized at the average fertilizer level in the Yangtze River basin with urea (195 kg N ha−1), superphosphate (75 kg P2O5 ha−1), potassium chloride (105 kg K2O ha−1), and borax (9 kg boron ha−1). Approximately 60% of the nitrogen fertilizer was applied at sowing and the remaining 40% of the nitrogen fertilizer was applied at the seedling stage, whereas phosphorus, potassium, and borax were all applied at sowing.The first experiment was conducted during the 2010-2011 and 2011-2012 growing seasons to evaluate the effects of plant density on seed yield and yield components. Conventional winter rapeseed variety Zhongshuang 11 (ZS 11) and the hybrid variety Zhongyouza 12 (ZYZ 12), two elite winter rapeseed varieties commonly grown in the Yangtze River basin, were used. The seeds were sown on 28 September in both 2010 and 2011. A split-plot design was used with three replicates. The main plots comprised five plant densities  population. The highest yield was obtained at a plant density of 58.5 × 104 plant ha−1, referred to as the high plant density (HPD) population for both varieties. The second experiment was a randomized complete block design with three replicates. The seeds were sown on 28 September in both 2012 and 2013. The plot area was 10 m long × 2 m wide and comprised 30 rows. A 1 m border surrounded each plot. The application rates of N, P2O5, and K2O were the same as those used in the 2010-2011 and 2011-2012 growing seasons.The second experiment was conducted during the 2012-2013 and 2013-2014 seasons to study physiological traits of different populations. In the first experiment, low seed yield was obtained at a plant density of 27.0 × 102) were sampled, and the yield components  at each plot were determined. Seed yield was determined by harvesting the plants of 5 m2 area in each plot, and the seed yields per unit area (ha−1) were calculated, with 9% standard moisture content.In 2010–2014 growing seasons, at maturity, plants per unit area . The MDA content was calculated according to the following formula: 6.453 × (A532 − A600) − 0.563 × A450.In 2012-2013 and 2013-2014 seasons, the chlorophyll and malondialdehyde contents in the leaves of HPD population and LPD population were determined. The frozen leaves (0.2 g) were first ground to a fine powder in liquid nitrogen, and chlorophyll was extracted after immersing the powder with cold acetone overnight at 4°C. The supernatant containing chlorophyll was generated after centrifugation at 10,000 ×g for 30 min. The residue was washed several times with cold acetone until it became colorless. The pooled supernatant was diluted to 10 mL with acetone until the final acetone concentration was 80%. The chlorophyll content per fresh weight of leaves was calculated as previously described . The MDA2 concentration (Ci), and transpiration rate (Tr) were determined. The data were collected automatically every 2-3 min with 10 replications for every plot.In 2012-2013 and 2013-2014 seasons, the green leaf area was measured by passing the leaves through a LI-3100 leaf area meter  at 7-day intervals after peak anthesis. The gas exchange analysis was conducted in the LPD and HPD populations of two varieties using a Portable Photosynthesis System  on the leaves from 09:00 to 11:00. The net photosynthetic rates (Pn), stomatal conductance (Gs), intercellular COAt the seed-filling stage, fifty pods on the main inflorescences and all of the branches were randomly sampled to measure the pod length and width, and the pod wall area was calculated according to Clarke (1978) . The pod2) in each plot were randomly selected, and the aerial parts were collected. The aerial parts were separated into stems, pod walls, and seeds and air dried for approximately 1 month to record dry biomass. The RUE was calculated as the ratio of above ground total dry weight at maturity to intercepted radiation during the flowering stage to maturity [Canopy radiation interception was measured at 7-day intervals from flowering stage to maturity using SunScan Canopy Analysis System . To measure the transmitted radiation, the 1 m probe was placed perpendicular to rows near soil surface for each plot. Another sensor (model BF5) was located outside the canopy for measurement of incident photosynthetically active radiation (PAR) , 36. Meamaturity .Different aerial organs at maturity at different densities were ground into powder, and an appropriate amount of plant material was used to determine the total nitrogen content using a modified Kjeldahl digestion method . The nitRoot digging was performed according to Majdi (1996) . The dynp = 0.05 using the Statistix 8 software. Significant pairwise differences between the mean values were identified using Duncan's multiple range tests (p < 0.05) in SPSS software . The mean values were separated using Duncan's multiple range test. All statistical determinations were made at p = 0.05. Correlations between the seed yield and pod numbers per unit area, seeds per pod, and 1000-seed weight in different plant densities were analyzed in 2010–2012 growing seasons, and a correlation analysis was performed to determine the relationships between seed yield and dry matter weight, radiation use efficiency, nitrogen utilization efficiency, and nitrogen harvest index in 2012–2014 seasons [We performed multiway ANOVA with critical values of  seasons .4 plant ha−1, the pod numbers per unit area of ZS 11 and ZYZ 12 varieties increased significantly at 48.0 × 104 plant ha−1 and 58.5 × 104 plant ha−1, respectively, and the maximum pod numbers per unit area were obtained at a plant density of 58.5 × 104 plant ha−1 for both varieties  .The highest and lowest values of the seed yields per plot were obtained at 58.5 × 10 = 0.78) , whereasThe chlorophyll content in the leaves decreased more rapidly in HPD than in LPD, and HPD showed a lower chlorophyll content Figures . HoweverThe GLAI in both HPD and LPD rapidly decreased after peak anthesis, and this value was lower in HPD than in LPD after 14 DAPA. During the 2012-2013 season, the GLAI from 0 to 28 days after peak anthesis in HPD decreased 85.5% and 84.7% in ZS 11 and ZYZ 12, respectively, whereas the GLAI in LPD decreased 64.0% and 69.3% in ZS 11 and in ZYZ 12, respectively . During 2 concentration (Ci), and transpiration rate (Tr) of leaves decreased rapidly after flowering, whereas the values declined rapidly in the high-yield population 21 days after peak anthesis –6(a)–In both seasons, the photosynthetic rate (Pn), stomatal conductance (Gs), intercellular COHigh plant density population had slightly lower accumulated incident radiation than the low plant density population owing to their shorter growth duration in two growing seasons in two varieties .However, the intercepted radiation was significantly higher in HPD population corresponding to their LPD populations. It is interesting that the higher canopy radiation interception in HPD population was due to the higher PAI. Compared with LPD, the dry matter weight in HPD increased 42.3% and 47.4% in ZS 11 during the 2012-2013 and 2013-2014 seasons, respectively, and the dry matter weight in ZYZ 12 increased 46.7% and 55.1%, respectively. In 2012-2013 and 2013-2014 seasons, HPD population had 18.7% and 24.3% higher RUE than LPD population in ZS 11, respectively. HPD population had 20.5% and 38.1% higher RUE than LPD population in ZYZ 12, respectively. The ANOVA results showed that the incident radiation, intercepted radiation, intercepted percent, total dry weight, and radiation use efficiency were all significantly or extremely significantly affected not only by the year, variety, and plant density but also by plant interactions.The nitrogen utilization efficiency increased 25.8% and 24.2% in HPD of ZS 11, respectively, and 14.0% and 43.7% in HPD of ZYZ 12 during the 2012-2013 and 2013-2014 seasons, respectively . The nitR2 = 0.83, R2 = 0.66, R2 = 0.79, and R2 = 0.86, resp.)  .For both HPD and LPD populations in the two varieties, the root length, root tips, root surface area, and root volume per unit area declined after peak anthesis , but theDuring the 2012-2013 season, these values decreased by 78.3%, 43.9%, 64.5%, and 45.3%, respectively, at 28 DAPA compared with 0 DAPA in HPD of ZS 11, whereas a decrease of 68.9%, 41.9%, 61.5%, and 37.8%, respectively, was observed in LPD. The root parameters showed a decrease of 64.6%, 54.3%, 67.6%, and 49.5%, respectively, in HPD of ZYZ 12, whereas a decrease of 62.5%, 41.3%, 53.6%, and 39.0%, respectively, was observed in LPD. Similarly, during the 2013-2014 season, these root values at 28 DAPA decreased by 77.8%, 46.9%, 54.8%, and 43.8%, respectively, in HPD of ZS 11, but a lower reduction of 67.0%, 37.8%, 50.0%, and 42.4%, respectively, was observed in LPD. In HPD of ZYZ 12, these values decreased by 64.5%, 49.0%, 54.5%, and 52.1%, respectively, and a lower reduction of 55.7%, 40.2%, 48.1%, and 51.0%, respectively, was observed in LPD. The ANOVA results showed that the year, variety, and DAPA significantly affected the root length, root tips, root surface area, and root volume. Additionally, the interactions among these factors significantly affect root morphology.4 plant ha−1 to 58.5 × 104 plant ha−1 and decreases at the plant density of 69.0 × 104 plant ha−1. It is consistent that an increasing the number of plants per unit area is associated with a better use of arable land and better light interception, but this does not always result in higher yielding capacity [Brassica napus L.) is a crop with a complex aerial architecture that determines a light gradient over the foliage [In the present study, the seed yield of winter oilseed rape can be effectively increased by increasing plant density from 27.0 × 10capacity , 44–50. capacity , the numcapacity , 47. Intcapacity . Oilseed foliage . As repo foliage . In the  foliage  and resu foliage  and Wang foliage , who sug foliage , which h foliage .Previous studies have also indicated that high yield is associated with dry matter production , 53. TheThe effects of five different plant densities were examined to optimize the population under modern cultivation systems and clarify the mechanism of high seed yield. The results indicated that a higher seed yield and optimal plant density were obtained after increasing the plant density to a certain range. In high plant density population, it showed a rapid decrease in GLAI and chlorophyll content as well as the rapid increase of MDA content after peak anthesis. The high yield highlighted the rapid increase of PAI and pod photosynthesis concomitant with accelerated leaf senescence after peak anthesis. The higher reduction in root morphological parameters, namely, root length, root tips, root surface area, and root volume, the higher accumulation in dry biomass, and higher N utilization efficiency in higher plant density treatment at peak anthesis suggested that that higher nutrient concentration could be available for shoot growth and seed filling.