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rTMS is an emerging treatment for major depressive disorder (MDD) refractory to medications and psychotherapy. The conventional target for rTMS in MDD is the dorsolateral prefrontal cortex (DLPFC). However, convergent evidence from lesion, stimulation, and neuroimaging studies suggests that the dorsomedial prefrontal cortex (DMPFC) may play a more central role in emotion regulation. We have recently demonstrated robust and potentially superior antidepressant properties for excitatory rTMS of the DMPFC. However, one of the enduring limitations of rTMS is the long duration of each treatment session under conventional protocols, which require ~40 minutes per day over 20-30 sessions for maximum efficacy using conventional 10 Hz stimulation. More recent studies have suggested that theta-burst stimulation (TBS) protocols can achieve stronger and more durable effects in markedly less time. Intermittent theta-burst stimulation (iTBS) generates robust and long-lasting excitatory effects with 600 pulses over ~3 min. Pilot studies have previously reported antidepressant effects with TBS over the DLPFC. However, TBS over the DMPFC has not previously been studied. Here we report robust antidepressant effects for a 7 min course of iTBS, administered bilaterally over the DMPFC with MRI-guidance at 120% resting motor threshold, over 20-30 sessions, in an open-label series of 40 patients with refractory MDD. Safety, efficacy, and tolerability are comparable to a 10 Hz rTMS protocol requiring 30-40 min of treatment. iTBS of the DMPFC may effectively reduce the duration (and cost) of rTMS >4-fold, thus increasing patient capacity per clinic and improving the overall accessibility of rTMS in refractory MDD.
Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.
An emerging recombinant norovirus GII.P16/GII.4 Sydney 2012 strain caused a gastroenteritis outbreak amongst attendees at a large health function in regional New South Wales, Australia. This was the third outbreak caused by the recombinant GII.P16/GII.4 Sydney 2012 strain in this region in 2017, which appears to be emerging as a common strain in the Hunter New England region.
Do DSM-IV diagnostic criteria for major depression (MD) in Chinese and Western women perform in a similar manner?
The CONVERGE study included interview-based assessments of women of Han Chinese descent with treated recurrent MD. Using Mplus software, we investigated the overall degree of between-sample measurement invariance (MI) for DSM-IV diagnostic criteria for MD in the CONVERGE sample and samples selected from four major Western studies from the USA and Europe matched to the inclusion criteria of CONVERGE. These analyses were performed one pair at a time. We then compared the results from CONVERGE paired with Western samples to those obtained when examining levels of MI between pairs of the Western samples.
Assuming a single factor model for the nine diagnostic criteria for MD, the level of MI based on global fit indexes observed between the CONVERGE and the four Western samples was very similar to that seen between the Western samples. Comparable results were obtained when using a two-factor structure for MI testing when applied to the 14 diagnostic criteria for MD disaggregated for weight, appetite, sleep, and psychomotor changes.
Despite differences in language, ethnicity and culture, DSM criteria for MD perform similarly in Chinese women with recurrent MD and comparable subjects from the USA and Europe. The DSM criteria for MD may assess depressive symptoms that are relatively insensitive to cultural and ethnic differences. These results support efforts to compare findings from depressed patients in China and Western countries.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
The symptoms of major depression (MD) are clinically diverse. Do they form coherent factors that might clarify the underlying nature of this important psychiatric syndrome?
Symptoms at lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years with recurrent DSM-IV MD. Exploratory factor analysis (EFA) and confirmatoryfactor analysis (CFA) were performed in Mplus in random split-half samples.
The preliminary EFA results were consistently supported by the findings from CFA. Analyses of the nine DSM-IV MD symptomatic A criteria revealed two factors loading on: (i) general depressive symptoms; and (ii) guilt/suicidal ideation. Examining 14 disaggregated DSM-IV criteria revealed three factors reflecting: (i) weight/appetite disturbance; (ii) general depressive symptoms; and (iii) sleep disturbance. Using all symptoms (n = 27), we identified five factors that reflected: (i) weight/appetite symptoms; (ii) general retarded depressive symptoms; (iii) atypical vegetative symptoms; (iv) suicidality/hopelessness; and (v) symptoms of agitation and anxiety.
MD is a clinically complex syndrome with several underlying correlated symptom dimensions. In addition to a general depressive symptom factor, a complete picture must include factors reflecting typical/atypical vegetative symptoms, cognitive symptoms (hopelessness/suicidal ideation), and an agitated symptom factor characterized by anxiety, guilt, helplessness and irritability. Prior cross-cultural studies, factor analyses of MD in Western populations and empirical findings in this sample showing risk factor profiles similar to those seen in Western populations suggest that our results are likely to be broadly representative of the human depressive syndrome.
Previous studies support Beck's cognitive model of vulnerability to depression. However, the relationship between his cognitive triad and other clinical features and risk factors among those with major depression (MD) has rarely been systematically studied.
The three key cognitive symptoms of worthlessness, hopelessness and helplessness were assessed during their lifetime worst episode in 1970 Han Chinese women with recurrent MD. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.
Compared to patients who did not endorse the cognitive trio, those who did had a greater number of DSM-IV A criteria, more individual depressive symptoms, an earlier age at onset, a greater number of episodes, and were more likely to meet diagnostic criteria for melancholia, postnatal depression, dysthymia and anxiety disorders. Hopelessness was highly related to all the suicidal symptomatology, with ORs ranging from 5.92 to 6.51. Neuroticism, stressful life events (SLEs) and a protective parental rearing style were associated with these cognitive symptoms.
During the worst episode of MD in Han Chinese women, the endorsement of the cognitive trio was associated with a worse course of depression and an increased risk of suicide. Individuals with high levels of neuroticism, many SLEs and high parental protectiveness were at increased risk for these cognitive depressive symptoms. As in Western populations, symptoms of the cognitive trio appear to play a central role in the psychopathology of MD in Chinese women.
The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms.
We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD.
Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9–6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt.
This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.
Studies conducted in Europe and the USA have shown that co-morbidity between major depressive disorder (MDD) and anxiety disorders is associated with various MDD-related features, including clinical symptoms, degree of familial aggregation and socio-economic status. However, few studies have investigated whether these patterns of association vary across different co-morbid anxiety disorders. Here, using a large cohort of Chinese women with recurrent MDD, we examine the prevalence and associated clinical features of co-morbid anxiety disorders.
A total of 1970 female Chinese MDD patients with or without seven co-morbid anxiety disorders [including generalized anxiety disorder (GAD), panic disorder, and five phobia subtypes] were ascertained in the CONVERGE study. Generalized linear models were used to model association between co-morbid anxiety disorders and various MDD features.
The lifetime prevalence rate for any type of co-morbid anxiety disorder is 60.2%. Panic and social phobia significantly predict an increased family history of MDD. GAD and animal phobia predict an earlier onset of MDD and a higher number of MDD episodes, respectively. Panic and GAD predict a higher number of DSM-IV diagnostic criteria. GAD and blood-injury phobia are both significantly associated with suicidal attempt with opposite effects. All seven co-morbid anxiety disorders predict higher neuroticism.
Patterns of co-morbidity between MDD and anxiety are consistent with findings from the US and European studies; the seven co-morbid anxiety disorders are heterogeneous when tested for association with various MDD features.
A phenotypic and genetic decline in dairy cattle fertility has been reported in several countries simultaneous to the increase in genetic merit for production. In addition, an increase in atypical milk progesterone (MP4) patterns, particularly extended luteal phases, has been observed by Royal et al. (2000). One such MP4 parameter; the interval from calving to commencement of luteal activity (CLA), has been studied by Royal et al. (2002a,b; 2003) and is reported to have moderate heritability (h2), an unfavourable genetic correlation (rA)to milk yield (rA; 0.36) and a favourable rA to calving interval and interval to first service, respectively (0.39, 0.53). Although CLA is a good indicator of onset of luteal activity (LA) postpartum (pp), it does not take account of subsequent ovarian activity. The objective of this study was to investigate an alternative MP4 parameter using the proportion of MP4 samples representing LA within the first 60 days pp in both British and Swedish dairy cows.
To estimate the magnitude and distribution of self-reported, acute gastrointestinal illness in a Canadian-based population, we conducted a retrospective, cross-sectional telephone survey of approximately 3500 randomly selected residents of the city of Hamilton (Ontario, Canada) from February 2001 to February 2002. The observed monthly prevalence was 10% (95% CI 9·94–10·14) and the incidence rate was 1·3 (95% CI 1·1–1·4) episodes per person-year; this is within the range of estimates from other developed countries. The prevalence was higher in females and in those aged <10 years and 20–24 years. Overall, prevalence peaked in April and October, but a different temporal distribution was observed for those aged <10 years. Although these data were derived from one community, they demonstrate that the epidemiology of acute gastrointestinal illness in a Canadian-based population is similar to that reported for other developed countries.
The effects of two UV irradiances (920 and 1200 mW m−2 weighted irradiance) on the conidia and germlings of the ARSEF 2575 and ARSEF 23 strains of M. anisopliae were studied. Conidia were exposed to the two irradiance levels for 1, 2, 3, 4, 6, or 8 h. The 30% increase (from 920 to 1200 mW m−2) in UV irradiance caused a significant decrease in culturability following all periods of exposure and reduced the 50% lethal time (TL50) 36% for strain 2575 and 48% for strain 23. Exposure to UV radiation of only 1 h caused a delay of several hours in the germination of surviving conidia. Longer periods of exposure delayed germination for days, demonstrating that, depending on the dose, the fungus may require a long period of time to recover and to resume germination. The results demonstrated the inability of the fungus to germinate during direct exposure to the UV-B portion of simulated sunlight. Both strains showed a transitory increase in UV tolerance during germination. The beginning of germination increased UV tolerance. However, starting on the 6th hour of germination, a decrease in tolerance was observed, indicating that UV tolerance varies as a function of physiological state and cell-cycle phase.
Reproductive performance of 714 Holstein Friesian dairy cows was monitored between October 1995 and June 1998 using thrice weekly milk progesterone determinations. Defined endocrine parameters such as interval to post-partum commencement of luteal activity, inter-ovulatory interval and length of luteal and inter-luteal intervals were used with a number of traditional measures of reproductive performance to investigate the current status of fertility in a sample of United Kingdom dairy herds. A comparison of the results of the 1995 to 1998 trial with those of a previous (1975 to 1982) milk progesterone database, which included 2503 lactations in British Friesian cows monitored using a similar milk sampling protocol, revealed a decline infertility between these periods.
Between 1975-1982 and 1995-1998, pregnancy rate to first service declined from 55·6% to 39·7% (P < 0·001), at a derived average rate approaching 1% per year. This decline was associated with an increase (P < 0·001) in the proportion of animals with one or more atypical ovarian hormone patterns from 32% to 44%. There was a significant (P < 0·001) increase in the incidence of delayed luteolysis during the first cycle post partum (delayed luteolysis type I; 7·3% to 18·2%) and during subsequent cycles (delayed luteolysis type II; 6·4% to 16·8%), although the incidence of prolonged anovulation post partům (delayed ovulation type I; 10·9% to 12·9%) and prolonged inter-luteal intervals (delayed ovulation type II; 12·9% to 10·6%) did not alter significantly. These changes resulted in an increase in mean luteal phase length from 12·9 (s.e. 0·09) to 14·8 (s.e. 0·17) days and an increase in inter-ovulatory interval from 20·2 (s.e. 0·1) to 22·3 (s.e. 0·2) days. The decline infertility was also reflected in traditional measures of fertility since although interval to first service remained relatively unchanged (74·0 (s.e. 0·4) to 77·6 (s.e. 1·1) days) calving interval lengthened from 370 (s.e. 2·2) to 390 (s.e. 2·5) days. Collectively these changes may have contributed to the decline in pregnancy rates observed over the last 20 years.
Cadmium zinc telluride crystals were grown by vertical Bridgman processes using in situ compdunding from high purity elements into pyrolytic boron nitride crucibles within sealed fused quartz ampoules containing cadmium vapor at a pressure of roughly one atmosphere. These conditions produce material having the low etch pit density, low precipitate density, high infrared transmission and high purity required for use as substrates for infrared focal plane detector arrays fabricated in epitaxial mercury cadmium telluride. Similar processes should be satisfactory for producing cadmium zinc telluride for gamma ray detectors.
Cadmium zinc telluride crystals were grown by vertical Bridgman processes using in situ compounding from high purity elements into pyrolytic boron nitride crucibles within sealed fused quartz ampoules containing cadmium vapor at a pressure of roughly one atmosphere. These conditions produce material having the low etch pit density, low precipitate density, high infrared transmission and high purity required for use as substrates for infrared focal plane detector arrays fabricated in epitaxial mercury cadmium telluride. Similar processes should be satisfactory for producing cadmium zinc telluride for gamma ray detectors.
The central role that growth hormone (GH) plays in growth and body composition has been documented extensively but in more recent times its role in a wide variety of functions, particularly in terms of reproduction and immune response, has begun to be explored more fully. In this chapter we describe the use of a model of GH deficiency involving passive immunization of rats with a specific antiserum to rat GH (anti-rGH) to investigate various aspects of development. The data provide evidence that GH plays a central role in development of both reproductive and immune functions in vivo, as well as demonstrating that GH plays a paradoxical role in stimulating adipocyte differentiation whilst enhancing lipid mobilization from mature adipocytes. Finally we describe the important autocrine/paracrine role that GH plays in the development of pituitary somatotrophs and its ability to sensitize the thyroid and ovary to the actions of TSH and the gonadotrophins, respectively.
Production and characterization of antibodies to rGH
Antisera to rGH were produced in sheep using a highly purified rGH preparation as immunogen. When examined in a radioimmunoassay, using 125I-rGH, cross-reactivity with other pituitary hormones was very low and could be explained in terms of their contamination with rGH (Madon et al., 1986). When the antiserum was assessed in vitro at the concentrations which could be achieved in vivo, it was capable of binding in excess of 1000 ng/ml of rGH. Since GH concentrations in the female rats used in this study are typically 100 ng/ml or lower, this indicated that the anti-rGH would effectively neutralize GH in vivo at the doses used.
The hypothesis that at least a subgroup of familial cases of schizophrenia could be due to a genetic defect on the X chromosome is supported by the observation of an excess of X-chromosome aneuploidies (XXX and XXY) among populations of patients with psychosis. The distal long arm, Xq27–q28, is a candidate region where linkage has been claimed to manic-depressive disorder and a fragile site has been associated with schizophrenia spectrum disorders. The present study excluded linkage to a large part of this region using four polymorphic probes and multipoint lod-score analysis in 10 families with multiple members with schizophrenia.
The use of exogenous hormone treatment as a means of increasing the efficiency of animal production has, in general, been rather poorly received by both the public and government agencies. This antipathy towards hormone treatment has tended to direct research effort into finding less contentious ‘hormonefree’ methods of improving animal production. Over the last 10 years, immunological manipulation of the endocrine system has emerged as an attractive possibility in this search. In this review we briefly outline three approaches under current consideration, whereby growth hormone (GH) concentrations or activity are modified. These methods involve immunological manipulation of GH release, use of antibodies as GH mimics and antibody-mediated enhancement of GH action.