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During the 2017 to 2019 growing seasons, samples of waterhemp and Palmer amaranth that had reportedly survived field-rate applications of protoporphyrinogen oxidase (PPO)–inhibiting herbicides were collected from the American Midwest and tested for target-site mutations known at the time to confer resistance. Target-site resistance was identified in nearly all (135 of 145) tested common waterhemp populations but in only 8 of 13 Palmer amaranth populations. Follow-up research on one population of Palmer amaranth (W-8), which tested negative for all such mutations, confirmed it was resistant to lactofen, with a magnitude of resistance comparable to that conferred by the ΔG210 PPO2 mutation. Gene sequences from both isoforms of PPO (PPO1 and PPO2) were compared between W-8 and known PPO inhibitor–sensitive sequence. A glycine-to-alanine substitution at the 399th amino acid position (G399A) of PPO2, recently identified to reduce target-site herbicide sensitivity, was observed in a subset of resistant W-8 plants. Because no missense mutation completely delimited resistant and sensitive sequences, we initially suspected the presence of a secondary, non-target-site resistance mechanism in this population. To isolate G399A, a segregating F2 population was produced and screened with a delimiting rate of lactofen. χ2 goodness-of-fit analysis of dead/alive ratings indicated single-locus inheritance of resistance in the F2 population, and molecular markers for the W-8 parental PPO2 coding region co-segregated tightly, but not perfectly, with resistance. More research is needed to fully characterize Palmer amaranth PPO inhibitor–resistance mechanisms, which appear to be more diverse than those found in common waterhemp.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are associated with increased mortality and healthcare costs. In 2007, a Veterans’ Affairs (VA) hospital implemented a MRSA nasal screening program, following a nationwide VA mandate, in an effort to reduce healthcare-associated MRSA infections.
To evaluate the correlation between the nasal screening results for MRSA and culture results of wound and tissue sites.
This retrospective study was conducted on inpatients at our VA hospital. Patients were included if they had undergone nasal screening for MRSA plus culture of a wound or tissue site within 30 days of hospital admission.
In total, 337 patients underwent nasal screening and wound culture and 211 underwent nasal screening and wound and tissue cultures. The prevalence of MRSA nasal colonization was 14.2% for wound samples and 15.2% for tissue samples. The sensitivities of MRSA nasal screening for detecting MRSA were 64.6% for wound cultures and 65.5% for tissue cultures. Specificities were 86.2% and 88.8% for wound and tissue cultures, respectively. The positive predictive values (PPVs) were 43.7% and 51.2% for wound and tissue cultures, respectively, and the negative predictive values (NPVs) were high at 93.6% and 93.5%, respectively.
In cases of wound or tissue samples for which culture results are pending, a negative MRSA nasal swab may be a component of the decision to withhold or discontinue MRSA-active agents.
Patients with non-Hodgkin's lymphoma and chronic lymphocytic leukaemia are at an elevated risk of further malignancy. Head and neck squamous cell carcinoma often presents with cervical lymph node metastasis, and can pose a diagnostic challenge in patients with non-Hodgkin's lymphoma or chronic lymphocytic leukaemia who may have pre-existing palpable neck nodes.
A retrospective case review of a health board was conducted to identify patients with head and neck squamous cell carcinoma with a previous diagnosis of non-Hodgkin's lymphoma or chronic lymphocytic leukaemia.
Four patients with head and neck squamous cell carcinoma that developed after non-Hodgkin's lymphoma or chronic lymphocytic leukaemia were identified. Two patients had a background of non-Hodgkin's lymphoma treated with chemotherapy. The remaining two patients had a background of chronic lymphocytic leukaemia under active surveillance. Three out of the four patients died within 30 months of diagnosis.
Head and neck squamous cell carcinoma following non-Hodgkin's lymphoma or chronic lymphocytic leukaemia is aggressive. A heightened clinical suspicion is essential to facilitate early diagnosis and treatment of head and neck squamous cell carcinoma in patients with dual pathology.
Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.
Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.
Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.
In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).
Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.
To study the association between school bonding dimensions (school commitment and school attachment) and current adolescent smoking in Chile, controlling for confounding variables using the Fifth Chilean School Population National Substance Use Survey, 2003 (CHSS-2003) dataset.
The CHSS-2003 is a stratified cross-sectional survey which gathers information about personal, familial, peer, school factors and cigarette use using a self-reported questionnaire. Complete data from 21,956 adolescent students for all the variables of interest were used in the analyses. An Exploratory Factor Analysis (EFA) was performed in order to test the construct validity of the questionnaire and create the main exposure and potential confounding variables. Multivariable logistic regression analyses were undertaken to study the association between school bonding and smoking.
The construct validity of the school attachment and school commitment scales was supported by the EFA. Multivariable analyses showed strong evidence that, after adjusting for factors from different domains, school commitment (student's good grades and school attendance) appears to have a clear inverse association with current smoking (OR=0.46; 95%CI: 0.38-0.56). On the other hand, school attachment (their feelings towards their school and their teachers) was not associated with adolescent smoking (OR=1.16; 95%CI: 0.88-1.53)
School commitment was strongly associated with current smoking. It is important to study further this variable with the aim of ascertaining whether or not interventions that improve school commitment may prevent or reduce smoking amongst adolescent students.
To evaluate once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy (50, 150 and 300mg/day) (acute and maintenance treatment) or adjunct treatment (150 and 300mg/day) in patients with MDD.
Eight (7 acute, 1 maintenance) placebo-controlled studies were analysed. Primary endpoints: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (acute); time from randomisation to depressed event (maintenance). Statistical analyses: ANCOVA for difference between quetiapine XR and placebo in LSM change in MADRS total score from randomisation to study end (LOCF; acute); hazard ratio (HR) for time to recurrence of a depressed event (maintenance).
Figure 1 shows treatment differences (95% CIs) for primary efficacy variable for the seven acute studies. Four monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00014) were significant in favour of quetiapine XR; Study D1448C00004 (monotherapy) was not. Studies D1448C00006 and D1448C00007 were significant in favour of adjunct quetiapine XR. Time from randomisation to depressed event (Study D1448C00005) significantly increased with quetiapine XR; HR (95% CI): 0.34(0.25, 0.46); p< 0.001; number of depressed events: 55, quetiapine XR; 132, placebo. Safety findings were consistent with the known tolerability profile of quetiapine.
Quetiapine XR consistently demonstrated antidepressant efficacy, with 6/7 acute studies positive in favour of quetiapine XR (monotherapy or adjunct). Quetiapine XR maintenance therapy significantly reduced risk of a depressed event, demonstrating relapse prevention. AstraZeneca funded
Few studies have been conducted looking at clinical features associated to treatment resistant depression (TRD) defined as failure to at least two consecutive antidepressant trials. The objective of this study was to identify clinical and demographic factors associated to TRD in a large sample of depressed patients who failed to reach response or remission after at least two consecutive adequate treatments.
A total of 702 patients with unipolar major depression were included in the analysis. 346 patients were considered as non resistant. The remaining 356 patients were considered as resistant with a HAM-D-17 score remaining ≥ 17 after 2 consecutive adequate trials. Cox regression models were used to examine the association between individual clinical variables and TRD.
Eleven variables were found to be associated with TRD. Anxiety comorbidity (p<0.001, OR=2.6), comorbid panic disorder (p<0.001, OR=2.6) and social phobia (p<0.008, OR=2.1), personality disorder (p<0.049, OR=1.7), suicidal risk (p<0.001, OR=2.2), severity (p<0.001, OR=1.7), melancholia (p<0.018, OR=1.5), a number of hospitalizations > 1 (p<0.003, OR=1.6), recurrent episodes (p<0.009, OR=1.5), early age of onset (p<0.009, OR=2.0) and non response to the first antidepressant received lifetime (p<0.019, OR=1.6).
Our findings provide a set of eleven relevant clinical variables associated to TRD which can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated to TRD.
Suicidal behaviour runs in families and the existence of genetic vulnerability to suicidality is well-established. Mental disorders, especially depression, are present in more of 90% of suicides. The incidence of treatment emergent suicidal ideation in major depression (MDD) varies from 4% to 20%, depending on the definition of suicidal ideation and sample characteristics.
In the present study, we further elucidated the impact of depression candidate genes in treatment emergent suicidal ideation in MDD. One hundred-seventy MDD patients were collected in the context of a resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. MDD subjects were genotyped for SNPs within the COMT gene, BDNF, DTNBP1, 5HT1A, 5HT2A, GNB3, GRIK4, PTGS1, PTGS2, CREB, and cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene. Response, remission and treatment resistance, as well as suicidality information derived from Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D) were recorded.
A quantitative and measure of suicidal behaviour was defined using the Hamilton rating scale (score 0 to 4) and the MINI-item (yes/no) on suicidality in a large cohort of depression cases. In addition, we tested for association with ‘serious suicidal attempts’ corresponding to a HAMD score of 4 (discrete trait analyses). Results of this candidate gene approach in treatment emergent suicidal ideation in MDD will be presented and discussed.
To evaluate the safety and efficacy of pregabalin in relieving the symptoms of GAD in patients ≥65 years of age.
This was a multicenter, randomized, flexible-dose, placebo-controlled, double-blind, parallel-group trial of pregabalin in the treatment of GAD. Randomization was 2:1, pregabalin:placebo. Patients underwent an 8-week double-blind, flexible-dosage (150-600 mg/d) treatment phase, including a 1-week dose-escalation period (50 mg/d to 150 mg/d). The primary efficacy assessment was change from baseline to endpoint-LOCF in HAM-A total score. Additionally, change from baseline to week 8 (observed cases) in HAM-A psychic and somatic factors was evaluated.
Mean age at GAD onset was 56 years; 77% of patients were women; mean age at enrollment was 72 years; mean duration of GAD was 17 years. Mean change from baseline in HAM-A total score was –12.84 (n=177) for the pregabalin group and –10.7 (n=96) for the placebo group (P=.0437). At week 8, patients treated with pregabalin had significant improvement in both the HAM-A psychic (–7.8 vs –6.3, P=.0111) and somatic (–6.6 vs –5.4, P=.0248) factors. The most common adverse events (AEs) among pregabalin-treated patients were dizziness (20.3%), somnolence (13.0%), headache (10.2%), and nausea (9.0%). Most AEs were mild-to-moderate and self-limiting. Discontinuation rates due to AEs were 10.7% and 9.4% in the pregabalin and placebo groups, respectively.
Pregabalin was effective in reducing the symptoms of GAD in patients aged 65 years and older, and it was safe and well tolerated in this population.
We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.
Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.
ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p<0.05). At Week 8, significantly more ESZ+EO patients had no clinically meaningful insomnia based on ISI</=7. Significant improvements with ESZ+EO (relative to PBO+EO) were observed in HAM-A total scores each week, and Weeks 4-10 excluding the insomnia item. ESZ+EO was significantly better at every timepoint on CGI-I (p<0.02); CGI-S was not different between treatments after Week 1. Median time to anxiolytic response was reduced with ESZ+EO based on HAM-A and CGI-I. HAM-A response and remission rates at Week 8 were higher with ESZ+EO, and HAM-D17 scores were improved at all timepoints (p<0.004). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and no treatment differences in sleep or daytime function. Significant treatment differences in anxiety and mood were maintained after discontinuation.
In this study, ESZ+EO was well tolerated and associated with improved sleep and daytime function without evidence of tolerance. Improvements in anxiety and mood were observed with ESZ+EO.
Support for this study provided by Sepracor Inc., Marlborough, MA.
Many association studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders including major depression (MDD). the BDNF gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. in the present study, we further elucidate the impact of BDNF in MDD patients with suicide risk and/or a personal history of suicide attempts.
Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for eight SNPs within the BDNF gene.
With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. However, in gender-specific analyses, we found haplotypic association with suicide risk in males, but not in females (rs925946-rs10501087-rs6265, rs10501087-rs6265-rs122733). the only single-marker association with suicide risk in males (rs908867) did not resist multiple testing correction. No significant associations were found in gender-specific analyses with regard to a personal history of suicide attempts.
In conclusion, we found two BDNF haplotypes significantly associated with suicide risk in male MDD patients. However, replication in larger well-defined cohorts is required to dissect this further.
Adolescent smoking remains as an important health problem in different countries. Understanding the factors involved in this behaviour may help to design and implement preventive programs.
To study the association between personal, familial, school and peer factors and smoking behaviour among Chilean adolescents.
To study the association between factors from four domains (personal, family, school and peers) and current smoking amongst adolescents performing secondary analyses of the Fifth Chilean School Population National Substance Use Survey (CHSS-2003) dataset.
The CHSS-2003 is a stratified cross-sectional survey which gathers information about personal, familial, school and peer factors and cigarette use using a self-reported questionnaire. Complete data from 21,956 students for all variables of interest were used in the analyses. Theory-driven hierarchical stepwise multivariable logistic regression analyses were performed to study the association between personal, familial, school and peer factors and smoking.
Results show that higher school commitment (OR = 0.46; 95%CI: 0.38–0.56), going home after school than not (OR = 0.69; 95%CI: 0.62–0.78), higher parental monitoring (OR = 0.62; 95%CI: 0.45–0.85), lower school aggressiveness (OR = 0.49; 95%CI: 0.33–0.73) and having a stronger negative opinion about drug use (OR = 0.40; 95%CI: 0.34–0.46) reduced the risk for smoking. However, the longer the time spent with friends the higher the risk for smoking (OR = 2.47; 95%CI: 2.08–2.94).
Results confirmed the importance of some personal, familial, school and peer factors in Chile. Prevention programs in Chile should include interventions aimed to strengthen factors such as school commitment and parental monitoring in order to prevent smoking amongst adolescents.
For the past several hundred years, Western science has helped shape the terms on which Europeans encountered and envisioned Africa and Africans. European preoccupations with the germ theory, what Michael Adas has called a European “machine ideology” arising from Western scientific and technological developments, the rise of scientific racism, and the “civilizing mission,” for example, as well as scientific interest in the archaeological, geological, and biological wealth of Africa have all influenced how Westerners have interacted with Africa and Africans. Moreover, belief in their own expertise and in the universal character of science led many Western scientists to believe that they could export Western science unmodified to Africa.
The multicenter, cross-sectional survey summarizes the current prescription patterns of psychopharmacological medications in patients with major depressive disorder (MDD) treated in European university psychiatric centers.
The study included a total of 1181 MDD patients who were recruited in 9 academic sites across 8 European countries. Socio-demographic, clinical, and psychopharmacological characteristics were collected within a detailed clinical interview and the current depressive symptom severity was measured by the Montgomery and Åsberg Depression Rating Scale (MADRS). Symptom reduction during the present MDD episode was analyzed by calculating retrospective MADRS scores. Descriptive statistics, analyses of variance (ANOVAs), and Spearman correlation analyses were performed to examine the impact of various features on the applied pharmacological strategies.
Regarding first-line antidepressant medication, the most frequently prescribed drug classes were selective serotonin reuptake inhibitors (SSRIs) (53.4%), serotonin-norepinephrine reuptake inhibitors (SNRIs) (23.6%), noradrenergic and specific serotonergic antidepressants (NaSSAs) (8.2%), tricyclic antidepressants (TCA) (5.1%), and the melatonergic antidepressant agomelatine (5.0%). The most commonly used individual antidepressants were escitalopram (18.4%), venlafaxine (15.2%), sertraline (12.9%), paroxetine (9.1%), mirtazapine (8.2%), duloxetine (7.0%), and fluoxetine (6.5%). Among the patients, 59.4% were treated with polypsychopharmaceutical medications (mean: 2 drugs) and for the number of individual drugs, we found a significant correlation with the present MADRS total score and the MADRS total score change during the current depressive episode.
Consistent with surveys investigating primarily municipal psychiatric treatment centers, we could replicate the observation that SSRIs are the most commonly used antidepressants in MDD for the first time for European university centers.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Coexistence of people and large carnivores depends on a complex combination of factors that vary geographically. Both the number and range of the Asiatic lion Panthera leo leo in the Greater Gir landscape, India, has increased since the 1990s. The challenge has been managing the success of conservation, with a particular focus on the spillover population ranging extensively in human-dominated landscapes. To understand the factors conducive to lion survival in this landscape, we undertook an interview-based survey. Overall, people expressed positive, tolerant attitudes towards lions. There was a distinct contrast between people's liking for lions (76.9% of respondents) compared to leopards (27.7%) in spite of greater depredation of livestock by lions (82.6%) than by leopards (17.4%). Younger people and respondents having greater awareness regarding lions expressed positive attitudes. Although community discussions on lions had a positive effect, there was no evidence that land-holding, management interventions, personal encounters with lions, or association of lions with religion affected attitudes. Respondents who had experienced livestock depredation tended to express negative attitudes. Respondents with positive attitudes towards lions favoured non-interventionist strategies for managing lions in the village areas. We advocate consideration of varied factors influencing tolerance of wildlife in conservation planning. We emphasize that site-specific human–wildlife conflict issues such as crop-foraging by wild ungulates and variation in attitudes towards different species should also be considered. Specifically, improved livestock management, motivation of local youth and their participation in awareness campaigns could all further strengthen the prevalent positive attitudes towards lions.
Convection is a highly turbulent, three dimensional process that is traditionally treated using a simple, local, time independent description. Convection is one of the largest sources of theoretical uncertainty in stellar modeling. We outline recent progress in studies using pulsating white dwarfs to constrain convection and calibrate mixing length theory.