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Unsustainable hunting, both illegal and legal, has led to the extirpation of many species. In the last 35 years giraffe Giraffa spp. populations have declined precipitously, with extinctions documented in seven African countries. Amongst the various reasons for these population declines, poaching is believed to play an important role in some areas. Giraffes are primarily hunted for consumption and for the use of their body parts as trophies and in traditional medicine. However, the socio-economic factors that correlate with the use of giraffe body parts are not well understood. We conducted our study in Tsavo Conservation Area, Kenya, which experiences high levels of poaching. We used semi-structured surveys amongst 331 households to document how giraffe body parts are typically acquired and their intended use (i.e. trophy, medicinal or consumptive). We then used logistic regression models to assess the correlations between nine socio-economic factors and the use of giraffe body parts. We found that giraffe body parts had mostly consumptive and trophy uses. One-time suppliers, opportunistic access and widely known markets were the most common means of acquiring giraffe body parts. Results from our models showed that three variables (gender: men, occupation: tourism worker, and land ownership) were correlated significantly and positively with the use of giraffe body parts. We describe the complex links between socio-economic factors and the use of giraffe body parts and highlight the importance of implementing mitigation measures adapted to local contexts to combat a challenge that many species of conservation concern are facing.
Children with developmental language disorder (DLD) show significant difficulties mastering language yet exhibit normal-range nonverbal intelligence, normal hearing and speech, and no neurological impairment. Deficits in sentence comprehension represent a major feature of school-age children’s language profile. So do memory limitations, including deficits in verbal working memory, controlled attention, and long-term memory. Though there is general consensus that the memory and comprehension deficits of these children relate in some fashion, the relationship has historically been unclear. In this chapter, we present the first conceptually integrated and empirically validated model of the sentence comprehension abilities of school-age children with DLD that describes the structural relationship among all these abilities.
Biomarkers may be useful endophenotypes for genetic studies if they share genetic sources of variation with the outcome, for example, with all-cause mortality. Australian adult study participants who had reported their parental survival information were included in the study: 14,169 participants had polygenic risk scores (PRS) from genotyping and up to 13,365 had biomarker results. We assessed associations between participants’ biomarker results and parental survival, and between biomarker results and eight parental survival PRS at varying p-value cut-offs. Survival in parents was associated with participants’ serum bilirubin, C-reactive protein, HDL cholesterol, triglycerides and uric acid, and with LDL cholesterol for participants’ fathers but not for their mothers. PRS for all-cause mortality were associated with liver function tests (alkaline phosphatase, butyrylcholinesterase, gamma-glutamyl transferase), metabolic tests (LDL and HDL cholesterol, triglycerides, uric acid), and acute-phase reactants (C-reactive protein, globulins). Association between offspring biomarker results and parental survival demonstrates the existence of familial effects common to both, while associations between biomarker results and PRS for mortality favor at least a partial genetic cause of this covariation. Identification of genetic loci affecting mortality-associated biomarkers offers a route to the identification of additional loci affecting mortality.
Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown.
This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people.
A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017).
Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.
Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17−93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04–1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.
Previous genetic studies on hair morphology focused on the overall morphology of the hair using data collected by self-report or researcher observation. Here, we present the first genome-wide association study (GWAS) of a micro-level quantitative measure of hair curvature. We compare these results to GWAS results obtained using a macro-level classification of observable hair curvature performed in the same sample of twins and siblings of European descent. Observational data were collected by trained observers, while quantitative data were acquired using an Optical Fibre Diameter Analyser (OFDA). The GWAS for both the observational and quantitative measures of hair curvature resulted in genome-wide significant signals at chromosome 1q21.3 close to the trichohyalin (TCHH) gene, previously shown to harbor variants associated with straight hair morphology in Europeans. All genetic variants reaching genome-wide significance for both GWAS (quantitative measure lead single-nucleotide polymorphism [SNP] rs12130862, p = 9.5 × 10–09; observational measure lead SNP rs11803731, p = 2.1 × 10–17) were in moderate to very high linkage disequilibrium (LD) with each other (minimum r2 = .45), indicating they represent the same genetic locus. Conditional analyses confirmed the presence of only one signal associated with each measure at this locus. Results from the quantitative measures reconfirmed the accuracy of observational measures.
Mapping genetic risk factors for endometriosis continues from early studies on women’s health initiated by Nick Martin and Susan Treloar. Their initial recruitment of endometriosis cases and family members received a major boost and became a flagship project within the Cooperative Research Centre (CRC) for the Discovery of Common Human Disease. We extended the study through a formal collaboration with Professor Stephen Kennedy and his group in Oxford. Our first joint scientific meeting was held in Brisbane and was sadly memorable as the day the planes were flown into the Twin Towers in New York. Our initial collaboration expanded into the International Endometriosis Genetics Consortium (IEGC). The IEGC now has 15 groups around the world, and the most recent meta-analysis will be published this year.
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 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
Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.
Subjects and methods
We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.
Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.
Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.
To evaluate efficacy and tolerability of quetiapine XR monotherapy in patients with MDD.
Data were analysed from two 6-week, multicentre, double-blind, placebo-controlled studies (D1448C00001, D1448C00002), prospectively designed to be pooled. Outpatients received quetiapine XR 150mg/day (n=315), 300mg/day (n=323), placebo (n=330). Primary outcome: change at Week 6 in MADRS total scores. Other assessments: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.
Quetiapine XR 150mg/day and 300mg/day reduced MADRS total scores at Week 6 (-14.7 and -14.7; p< 0.001) versus placebo (-11.1); significant reductions were also seen at Week 1 (p< 0.001).
Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender, age or depression severity.
Quetiapine XR demonstrated consistent improvements in MADRS items: both doses significantly improved 8/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 52.7% (p< 0.001), 49.5% (p< 0.001) versus 33.0%; MADRS remission (total score ≤10) was 33.7% (p< 0.01), 34.7% (p< 0.01) versus 24.2% for quetiapine XR 150mg/day and 300mg/day and placebo, respectively. Quetiapine XR 150mg/day and 300mg/day improved HAM-A total scores versus placebo at Week 1 (-4.6 [p< 0.01], -4.7 [p< 0.01], -3.6) and Week 6 (-8.1 [p< 0.001], -7.9 [p< 0.001], -6.2). Common AEs (≥10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine XR.
In patients with MDD, quetiapine XR monotherapy improved a broad range of depressive symptoms, with improvements seen from Week 1. Quetiapine XR was generally well tolerated.
Medication non-compliance is common in the treatment of depression, particularly in Asia.
1) To describe the frequency and factors associated with medication non-compliance. 2) To study the influence of non-compliance on treatment outcomes.
Nine hundred and nine in- and out-patients from Asia presenting with a new or first episode of major depressive disorder were enrolled in a 3-month prospective observational study. Clinical severity and quality of life were assessed, using Hamilton Depression Scale (HAMD-17), Clinical Global Impression Severity (CGI-S), and EuroQoL measures (EQ-5D and EQ-VAS). Medication compliance was also assessed by the investigator and patient. Linear and logistic multiple regression models were used to analyze the consequences of non-compliance.
The proportion of non-compliant patients as assessed by the investigator was 16%. Sociodemographic factors and clinical severity were not associated with compliance at baseline. Regression models showed that medication non-compliance was associated with worse depression severity (difference in HAMD-17 -3.98; 95% CI -5.10, -2.87) and overall clinical severity (CGI-S difference -0.46; 95%CI -0.68, -0.24) at three months. Medication non-compliance was also associated with lower quality of life at three months (EQ-VAS difference -7.47; 95%CI -11.13, - 3.82) and EQ-5D score difference -0.08; 95%CI -0.1, -0.04)). Compliant patients had higher odds of response (odds ratio (OR) 3.18; 95% CI 1.98, 5.10) and remission (OR 3.94; 95% CI 2.42, 6.43) compared with non-compliant patients.
Patients non-compliant with medication had worse 3-month outcomes in terms of depression severity, quality of life, and response and remission rates, compared with compliant patients.
The analysis of medication discontinuation may allow the comparison of the effectiveness of different medications and may help us understand treatment patterns in depression. Clinical guidelines recommend at least six months of antidepressant maintenance treatment for major depressive disorder (MDD).
To determine the duration of antidepressant treatment in Asian patients treated with antidepressants for a major depressive episode and to understand the reasons and factors associated with discontinuation.
Nine hundred and nine in- and out-patients from Asia, of which 569 started an antidepressant medication at the baseline visit, presenting with a new or first episode of MDD were enrolled in a 3-month prospective observational study. The Kaplan-Meier method and Cox models were used to estimate discontinuation rates and factors associated with discontinuation. Survival analysis with competing risks was used to analyze the influence of different reasons for discontinuation.
Of the 569 patients included in the study, 430 (75.6%) were evaluated at three months and analyzed. Of them, 242 (56%) discontinued the treatment during the three months follow-up and 188 maintained it. Of the overall sample, half of the patients discontinued the medication within 70 days. The most frequent reason for discontinuation was inadequate response (n=155, 64%), followed by adequate response (n=62, 26%). A relatively high proportion of patients with adequate response (30% at 130 days) discontinued the medication. Country and type of antidepressant were associated with medication discontinuation.
Medication discontinuation in Asian patients with depression is high, even for patients who respond adequately to treatment.
The aims of this study were to determine the presence of painful physical symptoms (PPS) and its impact on depression outcomes in different gender and age groups.
Three hundred in- and out-patients from China presenting with a new or first episode of major depressive disorder were enrolled in a 3- month prospective observational study from Asia (N=909). Hamilton Depression Scale (HAMD-17), Clinical Global Impression Severity (CGI-S), EuroQoL and the pain-related items of the Somatic Symptom Inventory were administered. Patients were classified into three age groups (<40, n=119; =40-<60, n=133; =60, n=48). Linear and logistic regression models were fitted to assess the relationship between PPS at baseline and outcomes.
Older patients had higher HAMD-17 severity at baseline. HAMD score was 25.9 (SD 6.1) in =60 vs. 22.5 (SD 5.0) in <40 and 24.8 (SD 5.2) in =40-<60. There were no statistically significant differences in the proportion of patients with PPS across gender and age groups. During follow-up, depression severity improved. There were no statistically significant differences in the degree of improvement by gender, but there were differences by age group. Mean change in HAMD was -16.4 (95%CI -17.7;-15.1) for those <40, -19.9 (95%CI -21.1;-18.7) in 40-60 and - 20.3 (95%CI -22.6;-17.9) in >60. PPS positive patients had worse clinical and quality of life outcomes across genders and age groups.
The presence of painful physical symptoms is associated with a lower improvement in depression outcomes and a lower quality of life in patients with major depression across different gender and age groups.
Major depressive disorder (MDD) is the second leading cause of disability in China.
To analyze functioning during the course of treating MDD in China, Taiwan and Hong Kong.
To study the influence of pain and clinical remission on functioning.
This was a post-hoc analysis of a 6-month, prospective, observational study (n = 909) with 422 patients enrolled from China (n = 205; 48.6%), Taiwan (n = 199; 47.2%) and Hong Kong (n = 18; 4.2%). Functioning was measured with the Sheehan Disability Scale (SDS), pain with the Somatic Symptom Inventory, and severity of depression with the Quick Inventory of Depressive Symptomatology-Self Report 16 (QIDS). Patients were classified as having no pain, persistent pain (pain at any visit) or remitted pain (pain only at baseline). A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning.
At baseline, 40% of the patients had painful physical symptoms. Patients with pain had a higher QIDS and lower SDS (P < 0.05) at baseline. At 6 months, patients with persistent pain had lower functioning (P < 0.05). The regression model confirmed that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no pain group.
Patients presenting with pain symptoms had lower functioning at baseline. At 6 months, pain persistence was associated with significantly lower functioning as measured by the SDS. Clinical remission was associated with better functional outcomes. The course of pain was related to the likelihood of achieving remission.
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.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The completion of a laser safety course remains a core surgical curriculum requirement for otolaryngologists training in the UK. This project aimed to develop a comprehensive laser safety course utilising both technical and non-technical skills simulation.
Otolaryngology trainees and consultants from the West of Scotland Deanery attended a 1-day course comprising lectures, two high-fidelity simulation scenarios and a technical simulation of safe laser use in practice.
The course, and in particular the use of simulation training, received excellent feedback from otolaryngology trainees and consultants who participated. Both simulation scenarios were validated for future use in laser simulation.
The course has been recognised as a laser safety course sufficient for the otolaryngology Certificate of Completion of Training. To the authors’ knowledge, this article represents the first description of using in situ non-technical skills simulation training for teaching laser use in otolaryngology.