Objective: Symptom rating scales, which have been used historically in the assessment of psychiat... more Objective: Symptom rating scales, which have been used historically in the assessment of psychiatric disorders in clinical trials, are a necessary, but not sufficient, criterion for measuring treatment outcomes. Other domains of functioning (e.g. sense of well-being & life satisfaction), broadly conceptualized as quality of life (QOL), are increasingly recognized as clinically important. Despite this, fewer than 5% of randomized controlled treatment trials recently surveyed reported on QOL. The current analysis was undertaken to assess QOL findings from a range of sertraline treatment studies.
Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depress... more Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depression. The goal of this study was to develop and validate a brief instrument to screen for bipolar disorder in patients actively ill with major depression. The sample consisted of subjects who enrolled in the National Institute of Mental Health-Collaborative Program on the Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode of major depression and included 91 subjects with bipolar I major depression, 52 with bipolar II major depression, and 338 with unipolar major depression diagnosed according to Research Diagnostic Criteria. Most of the subjects were inpatients at the time of enrollment, and subjects were prospectively followed for up to 20 years. In order to create, test, and cross-validate the screening instrument, a split-sample data analytic procedure was performed. This procedure yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross-validation sample, and the bipolar II cross-validation sample. Each group included subjects with bipolar major depression and subjects with unipolar major depression. Within the bipolar I index sample, subjects with bipolar I major depression at study intake were compared with subjects with unipolar major depression at study intake on a pool of 59 sociodemographic and clinical candidate variables. The 3 variables showing the greatest disparity between bipolar I subjects and unipolar subjects were selected for the screen, the Screening Assessment of Depression-Polarity (SAD-P). The operating characteristics of the SAD-P were then examined within the bipolar I index sample, bipolar I cross-validation sample, and bipolar II cross-validation sample. The items selected for the screening instrument were (1) presence of delusions during the current episode of major depression, (2) number of prior episodes of major depression, and (3) family history of major depression or mania. The screen identified bipolar major depression with a sensitivity of 0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation sample, and 0.58 in the bipolar II cross-validation sample. With regard to misclassifying subjects with unipolar major depression, the screen provided a positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation sample. We suggest using the 3-item SAD-P as a preliminary screen for bipolar disorder in patients who present with an active episode of major depression.
Objective: Indirect evidence suggests that abnormalities in serotonergic function may be involved... more Objective: Indirect evidence suggests that abnormalities in serotonergic function may be involved in the pathogenesis of premenstrual dysphoric disorder. The goal of this study was to test the hypothesis of serotonergic deficiency in premenstrual dysphoric disorder by measuring the prolactin response to fenfluramine. Method: The authors administered the serotonin-releasing drug dl-fenfluramine in a placebo-controlled protocol to nine women with premenstrual dysphoric disorder and 11 healthy female volunteers in the luteal phase of the menstrual cycle. Results: Compared to the normal subjects, the women with premenstrual dysphoric disorder had a significantly blunted prolactin response to fenfluramine. Conclusions: Premenstrual dysphoric disorder appears to be associated with serotonergic deficiency.
Major depressive disorder is usually a recurring illness, and maintenance treatment is used to fo... more Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis. The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis. For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.
apparent innuence on sexu:ally·related behavior. The underlying mechanisms of lhese effects are s... more apparent innuence on sexu:ally·related behavior. The underlying mechanisms of lhese effects are slill unc!e<lr in humans. There is some information on the interaction belween estrogen and m:ajor neurotransmillers -mostly on the membrane receptor level and melabolism. fntracellul:lt genomic and non.genomic effects are still in a need to be unfolded. The direct effect of gonadal steroids on ct'ntrol nervous system (CNS) processes (with no neurotransmiller modulation) is still mostly unknown. lhough plausible. The interaction between the HPO system and other major honnonal systems (like the Hypolhalamo-Pituitary-Adrenal (HPA) and HP-thyroid (HPT) systems) and the impact of these internctions on mood and behavior need to be elucidated, as well as tbe similarities between estrogen and other gonadal sleroids and thyroid hormones, their effects on the eNS, llnd interaction with psychotropic medications. The direct effect of hypothalamic rchmsing 11Onnones and pituitary stimulating hormones arc also relatively neglected and might be found to be of import. An area that is just rccenlly taking off is the application of gonadal steroids and other reproductive-related honnones or their synthetic analogs, as psychotropic medications. independently or as ndjuncts to other psychotropic compounds. This development follows better understanding of biology :Ind pathobiology of reproductive-related hormones but also will contribute to enhancement of that knOWledge.
The recognition or detection of depressive symptoms and syndromes in patients with cancer is of v... more The recognition or detection of depressive symptoms and syndromes in patients with cancer is of value to the patient because his mental distress may respond to treatment, and to the clinician because some of the clinical complications or difficulties in diagnosis and treatment of the patient may be reduced. Many factors militate against the diagnosis of depressive syndromes in patients with cancer. These include problems with the application of standard sets of criteria for depression, the assumption on the part of medical staff, family, and patients that depression is a "natural" response and therefore not treatable, and the pressure on all involved to "think positive." Some ways of modifying the usual screening and diagnostic procedures for depressive disorders are suggested.
The Journal of Neuropsychiatry and Clinical Neurosciences, 1999
Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA... more Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA-approved psychopharmacologic treatment for aggression. In this study, 20 chronically aggressive hospitalized patients were administered 1 week of placebo followed by an open trial of increasing doses of propranolol. Patients who had an equivocal or definite clinical response were entered into an open add-on double-blind discontinuation study phase. Aggressive behavior was objectively documented throughout the study. After the open phase of the study, 7 patients had a greater than 50% decrease in aggressive behavior. Four patients entered the double-blind discontinuation phase. The clinical course of 3 of those patients was consistent with the positive response to propranolol. The results of this study are consistent with a therapeutic effect of propranolol in some patients with aggressive behavior. Further studies are indicated.
Proceedings of SPIE - The International Society for Optical Engineering, 2012
ABSTRACT The European Space Agency has funded e2v’s development of an image sensor for the visibl... more ABSTRACT The European Space Agency has funded e2v’s development of an image sensor for the visible instrument in the Euclid space telescope. Euclid has been selected for a medium class mission launch opportunity in 2020. The project aims to map the dark universe with two complementary methods; a galaxy red-shift survey and weak gravitational lensing using near infrared and visible instruments. The baseline for the visible instrument was to be the CCD203-82, which has been successfully flown on NASA’s Solar Dynamics Observatory. However, to optimise the device for Euclid, e2v have designed and manufactured the CCD273-84. This device has a higher-responsivity lower-noise amplifier, enhanced red response, parallel charge injection structures and narrower registers which improve low signal charge transfer efficiency. Development models for Euclid have been manufactured with a thinner gate dielectric than standard for improved tolerance to ionising radiation. This paper describes the imager sensor in detail and focuses on the novel aspects of the device, package and interface.
Proceedings of SPIE - The International Society for Optical Engineering, 2012
ABSTRACT Euclid is a medium class mission selected for launch in 2019, with a primary goal to stu... more ABSTRACT Euclid is a medium class mission selected for launch in 2019, with a primary goal to study the dark universe using the weak lensing and baryonic acoustic oscillations techniques. Weak lensing depends on accurate shape measurements, therefore it is beneficial that the effects of radiation-induced charge transfer inefficiency (CTI) in the Euclid CCD over the six year mission are understood and minimised. This paper describes the initial evaluation of the tolerance to radiation induced charge transfer inefficiency (CTI) of the CCD273 produced by e2v technologies plc, making comparisons with the previous CCD selected for Euclid the CCD203. The CCD273 benefits from the inclusion of a charge injection structure for trap suppression and a reduction in the register channel width. The improvement in tolerance to radiation induced serial CTI achieved by reducing the channel width from 50 μm to 20 μm was measured experimentally to be a factor of 1.7, which compares well to a factor of 1.9 found using a charge volume model
Fifty subjects at the New York facility of the National Institute of Mental Health Clinical Resea... more Fifty subjects at the New York facility of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression were evaluated for cross-sectional psychopathology and functional impairment at the 2-year followup by two professional raters, one blind and one with extensive knowledge of the subject&#39;s psychiatric history and course of illness and treatment (the cohort rater). Ratings were made on the change version of the Schedule for Affective Disorders and Schizophrenia. Interrater reliability, as tested using the intraclass correlation coefficient, was quite good for most of the symptom ratings and fair on measures of functional impairment and social functioning. However, there was a consistent tendency for the blind rater to score higher levels on symptoms of depression and anxiety than the informed cohort rater. Reasons for disagreement in different symptom areas are discussed. Using only the informed rater provides a very adequate picture of severity and patterns of psychopathology on a cross-sectional basis.
Two groups of returnees to Orthodox Judaism who were among Lubavitcher Hasidim attending an outpa... more Two groups of returnees to Orthodox Judaism who were among Lubavitcher Hasidim attending an outpatient mental health center were studied to investigate a relief effect upon returning. One group manifested lifelong serious psychopathology, and the members of the comparison group, who had undergone similar religious transition, had sought help for adjustment-type problems. The psychopathology manifested prior to religious change persisted for those who had exhibited a lifelong history of pathology, even after the radical transition. The lack of a relief effect and the lifestyles possibly unique to Lubavitcher Hasidim are discussed.
The predictive value of early functional improvement for treatment success at week 8 was assessed... more The predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD). Data were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7), and functional/depression remission (SDS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model. The proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958-0.970; all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Discussion Patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.
The use of sets of diagnostic criteria and excellent structured clinical interviews will not resu... more The use of sets of diagnostic criteria and excellent structured clinical interviews will not result in data that is adequate for valid diagnoses or for dimensional measures if the rater collecting the data does not have adequate clinical skills. In the absence of biological measures or tests we are dependent on the rater&#39;s diagnostic and interviewing skills-both with subjects about themselves and with family informants asked to provide information about others. Best estimate diagnosticians (who usually have more experience and training) cannot compensate for inadequate or incorrect information and may even be misled by the information provided to them. In reviewing videotaped interviews sent by &quot;trained&quot; and &quot;experienced&quot; raters who were seeking &quot;certification,&quot; approximately 40% of the raters were judged to have failed to conduct an adequate diagnostic evaluation. Principal Investigators should make every effort to assure that their diagnostic data is being collected by experienced and well-trained professional raters and that the raters&#39; ongoing work is subjected to close supervision and review.
Acta Crystallographica Section D Biological Crystallography, 2005
Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively... more Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively carried out using a high-throughput workflow implemented in the Oxford Protein Production Facility. Initial crystallization screening is based on nanolitre-scale sitting-drop vapour-diffusion experiments (typically 100 nl of protein plus 100 nl of reservoir solution per droplet) which use standard crystallization screening kits and 96-well crystallization plates. For 294 K crystallization trials the barcoded crystallization plates are entered into an automated storage system with a fully integrated imaging system. These plates are imaged in accordance with a pre-programmed schedule and the resulting digital data for each droplet are harvested into a laboratory informationmanagement system (LIMS), scored by crystal recognition software and displayed for user analysis via a web-based interface. Currently, storage for trials at 277 K is not automated and for imaging the crystallization plates are fed by hand into an imaging system from which the data enter the LIMS. The workflow includes two procedures for nanolitre-scale optimization of crystallization conditions: (i) a protocol for variation of pH, reservoir dilution and protein:reservoir ratio and (ii) an additive screen. Experience based on 592 crystallization projects is reported. # 2005 International Union of Crystallography Printed in Denmark -all rights reserved conference papers Acta Cryst. (2005). D61, 651-657 Walter et al. High-throughput nanolitre crystallization experiments 655 Figure 5
Volunteers who claimed they were "healthy and normal" and did not reveal any physical o... more Volunteers who claimed they were "healthy and normal" and did not reveal any physical or mental abnormality or medication use during brief structured interviews underwent detailed structured interviews with the Schedule for Affective Disorders and Schizophrenia. Diagnoses were based on the Research Diagnostic Criteria (RDC), and family history was determined with the Family History RDC. Of the 121 volunteers, 16.5% met criteria for diagnoses of current mental disorders. Of the 104 without current DSM-III axis I diagnoses, 35.6% had past histories and 39.4% had family histories of mental illness. These results emphasize the need for thorough assessment of "normal volunteers."
Objective: Symptom rating scales, which have been used historically in the assessment of psychiat... more Objective: Symptom rating scales, which have been used historically in the assessment of psychiatric disorders in clinical trials, are a necessary, but not sufficient, criterion for measuring treatment outcomes. Other domains of functioning (e.g. sense of well-being & life satisfaction), broadly conceptualized as quality of life (QOL), are increasingly recognized as clinically important. Despite this, fewer than 5% of randomized controlled treatment trials recently surveyed reported on QOL. The current analysis was undertaken to assess QOL findings from a range of sertraline treatment studies.
Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depress... more Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depression. The goal of this study was to develop and validate a brief instrument to screen for bipolar disorder in patients actively ill with major depression. The sample consisted of subjects who enrolled in the National Institute of Mental Health-Collaborative Program on the Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode of major depression and included 91 subjects with bipolar I major depression, 52 with bipolar II major depression, and 338 with unipolar major depression diagnosed according to Research Diagnostic Criteria. Most of the subjects were inpatients at the time of enrollment, and subjects were prospectively followed for up to 20 years. In order to create, test, and cross-validate the screening instrument, a split-sample data analytic procedure was performed. This procedure yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross-validation sample, and the bipolar II cross-validation sample. Each group included subjects with bipolar major depression and subjects with unipolar major depression. Within the bipolar I index sample, subjects with bipolar I major depression at study intake were compared with subjects with unipolar major depression at study intake on a pool of 59 sociodemographic and clinical candidate variables. The 3 variables showing the greatest disparity between bipolar I subjects and unipolar subjects were selected for the screen, the Screening Assessment of Depression-Polarity (SAD-P). The operating characteristics of the SAD-P were then examined within the bipolar I index sample, bipolar I cross-validation sample, and bipolar II cross-validation sample. The items selected for the screening instrument were (1) presence of delusions during the current episode of major depression, (2) number of prior episodes of major depression, and (3) family history of major depression or mania. The screen identified bipolar major depression with a sensitivity of 0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation sample, and 0.58 in the bipolar II cross-validation sample. With regard to misclassifying subjects with unipolar major depression, the screen provided a positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation sample. We suggest using the 3-item SAD-P as a preliminary screen for bipolar disorder in patients who present with an active episode of major depression.
Objective: Indirect evidence suggests that abnormalities in serotonergic function may be involved... more Objective: Indirect evidence suggests that abnormalities in serotonergic function may be involved in the pathogenesis of premenstrual dysphoric disorder. The goal of this study was to test the hypothesis of serotonergic deficiency in premenstrual dysphoric disorder by measuring the prolactin response to fenfluramine. Method: The authors administered the serotonin-releasing drug dl-fenfluramine in a placebo-controlled protocol to nine women with premenstrual dysphoric disorder and 11 healthy female volunteers in the luteal phase of the menstrual cycle. Results: Compared to the normal subjects, the women with premenstrual dysphoric disorder had a significantly blunted prolactin response to fenfluramine. Conclusions: Premenstrual dysphoric disorder appears to be associated with serotonergic deficiency.
Major depressive disorder is usually a recurring illness, and maintenance treatment is used to fo... more Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis. The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis. For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.
apparent innuence on sexu:ally·related behavior. The underlying mechanisms of lhese effects are s... more apparent innuence on sexu:ally·related behavior. The underlying mechanisms of lhese effects are slill unc!e<lr in humans. There is some information on the interaction belween estrogen and m:ajor neurotransmillers -mostly on the membrane receptor level and melabolism. fntracellul:lt genomic and non.genomic effects are still in a need to be unfolded. The direct effect of gonadal steroids on ct'ntrol nervous system (CNS) processes (with no neurotransmiller modulation) is still mostly unknown. lhough plausible. The interaction between the HPO system and other major honnonal systems (like the Hypolhalamo-Pituitary-Adrenal (HPA) and HP-thyroid (HPT) systems) and the impact of these internctions on mood and behavior need to be elucidated, as well as tbe similarities between estrogen and other gonadal sleroids and thyroid hormones, their effects on the eNS, llnd interaction with psychotropic medications. The direct effect of hypothalamic rchmsing 11Onnones and pituitary stimulating hormones arc also relatively neglected and might be found to be of import. An area that is just rccenlly taking off is the application of gonadal steroids and other reproductive-related honnones or their synthetic analogs, as psychotropic medications. independently or as ndjuncts to other psychotropic compounds. This development follows better understanding of biology :Ind pathobiology of reproductive-related hormones but also will contribute to enhancement of that knOWledge.
The recognition or detection of depressive symptoms and syndromes in patients with cancer is of v... more The recognition or detection of depressive symptoms and syndromes in patients with cancer is of value to the patient because his mental distress may respond to treatment, and to the clinician because some of the clinical complications or difficulties in diagnosis and treatment of the patient may be reduced. Many factors militate against the diagnosis of depressive syndromes in patients with cancer. These include problems with the application of standard sets of criteria for depression, the assumption on the part of medical staff, family, and patients that depression is a "natural" response and therefore not treatable, and the pressure on all involved to "think positive." Some ways of modifying the usual screening and diagnostic procedures for depressive disorders are suggested.
The Journal of Neuropsychiatry and Clinical Neurosciences, 1999
Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA... more Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA-approved psychopharmacologic treatment for aggression. In this study, 20 chronically aggressive hospitalized patients were administered 1 week of placebo followed by an open trial of increasing doses of propranolol. Patients who had an equivocal or definite clinical response were entered into an open add-on double-blind discontinuation study phase. Aggressive behavior was objectively documented throughout the study. After the open phase of the study, 7 patients had a greater than 50% decrease in aggressive behavior. Four patients entered the double-blind discontinuation phase. The clinical course of 3 of those patients was consistent with the positive response to propranolol. The results of this study are consistent with a therapeutic effect of propranolol in some patients with aggressive behavior. Further studies are indicated.
Proceedings of SPIE - The International Society for Optical Engineering, 2012
ABSTRACT The European Space Agency has funded e2v’s development of an image sensor for the visibl... more ABSTRACT The European Space Agency has funded e2v’s development of an image sensor for the visible instrument in the Euclid space telescope. Euclid has been selected for a medium class mission launch opportunity in 2020. The project aims to map the dark universe with two complementary methods; a galaxy red-shift survey and weak gravitational lensing using near infrared and visible instruments. The baseline for the visible instrument was to be the CCD203-82, which has been successfully flown on NASA’s Solar Dynamics Observatory. However, to optimise the device for Euclid, e2v have designed and manufactured the CCD273-84. This device has a higher-responsivity lower-noise amplifier, enhanced red response, parallel charge injection structures and narrower registers which improve low signal charge transfer efficiency. Development models for Euclid have been manufactured with a thinner gate dielectric than standard for improved tolerance to ionising radiation. This paper describes the imager sensor in detail and focuses on the novel aspects of the device, package and interface.
Proceedings of SPIE - The International Society for Optical Engineering, 2012
ABSTRACT Euclid is a medium class mission selected for launch in 2019, with a primary goal to stu... more ABSTRACT Euclid is a medium class mission selected for launch in 2019, with a primary goal to study the dark universe using the weak lensing and baryonic acoustic oscillations techniques. Weak lensing depends on accurate shape measurements, therefore it is beneficial that the effects of radiation-induced charge transfer inefficiency (CTI) in the Euclid CCD over the six year mission are understood and minimised. This paper describes the initial evaluation of the tolerance to radiation induced charge transfer inefficiency (CTI) of the CCD273 produced by e2v technologies plc, making comparisons with the previous CCD selected for Euclid the CCD203. The CCD273 benefits from the inclusion of a charge injection structure for trap suppression and a reduction in the register channel width. The improvement in tolerance to radiation induced serial CTI achieved by reducing the channel width from 50 μm to 20 μm was measured experimentally to be a factor of 1.7, which compares well to a factor of 1.9 found using a charge volume model
Fifty subjects at the New York facility of the National Institute of Mental Health Clinical Resea... more Fifty subjects at the New York facility of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression were evaluated for cross-sectional psychopathology and functional impairment at the 2-year followup by two professional raters, one blind and one with extensive knowledge of the subject&#39;s psychiatric history and course of illness and treatment (the cohort rater). Ratings were made on the change version of the Schedule for Affective Disorders and Schizophrenia. Interrater reliability, as tested using the intraclass correlation coefficient, was quite good for most of the symptom ratings and fair on measures of functional impairment and social functioning. However, there was a consistent tendency for the blind rater to score higher levels on symptoms of depression and anxiety than the informed cohort rater. Reasons for disagreement in different symptom areas are discussed. Using only the informed rater provides a very adequate picture of severity and patterns of psychopathology on a cross-sectional basis.
Two groups of returnees to Orthodox Judaism who were among Lubavitcher Hasidim attending an outpa... more Two groups of returnees to Orthodox Judaism who were among Lubavitcher Hasidim attending an outpatient mental health center were studied to investigate a relief effect upon returning. One group manifested lifelong serious psychopathology, and the members of the comparison group, who had undergone similar religious transition, had sought help for adjustment-type problems. The psychopathology manifested prior to religious change persisted for those who had exhibited a lifelong history of pathology, even after the radical transition. The lack of a relief effect and the lifestyles possibly unique to Lubavitcher Hasidim are discussed.
The predictive value of early functional improvement for treatment success at week 8 was assessed... more The predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD). Data were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7), and functional/depression remission (SDS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model. The proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958-0.970; all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Discussion Patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.
The use of sets of diagnostic criteria and excellent structured clinical interviews will not resu... more The use of sets of diagnostic criteria and excellent structured clinical interviews will not result in data that is adequate for valid diagnoses or for dimensional measures if the rater collecting the data does not have adequate clinical skills. In the absence of biological measures or tests we are dependent on the rater&#39;s diagnostic and interviewing skills-both with subjects about themselves and with family informants asked to provide information about others. Best estimate diagnosticians (who usually have more experience and training) cannot compensate for inadequate or incorrect information and may even be misled by the information provided to them. In reviewing videotaped interviews sent by &quot;trained&quot; and &quot;experienced&quot; raters who were seeking &quot;certification,&quot; approximately 40% of the raters were judged to have failed to conduct an adequate diagnostic evaluation. Principal Investigators should make every effort to assure that their diagnostic data is being collected by experienced and well-trained professional raters and that the raters&#39; ongoing work is subjected to close supervision and review.
Acta Crystallographica Section D Biological Crystallography, 2005
Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively... more Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively carried out using a high-throughput workflow implemented in the Oxford Protein Production Facility. Initial crystallization screening is based on nanolitre-scale sitting-drop vapour-diffusion experiments (typically 100 nl of protein plus 100 nl of reservoir solution per droplet) which use standard crystallization screening kits and 96-well crystallization plates. For 294 K crystallization trials the barcoded crystallization plates are entered into an automated storage system with a fully integrated imaging system. These plates are imaged in accordance with a pre-programmed schedule and the resulting digital data for each droplet are harvested into a laboratory informationmanagement system (LIMS), scored by crystal recognition software and displayed for user analysis via a web-based interface. Currently, storage for trials at 277 K is not automated and for imaging the crystallization plates are fed by hand into an imaging system from which the data enter the LIMS. The workflow includes two procedures for nanolitre-scale optimization of crystallization conditions: (i) a protocol for variation of pH, reservoir dilution and protein:reservoir ratio and (ii) an additive screen. Experience based on 592 crystallization projects is reported. # 2005 International Union of Crystallography Printed in Denmark -all rights reserved conference papers Acta Cryst. (2005). D61, 651-657 Walter et al. High-throughput nanolitre crystallization experiments 655 Figure 5
Volunteers who claimed they were "healthy and normal" and did not reveal any physical o... more Volunteers who claimed they were "healthy and normal" and did not reveal any physical or mental abnormality or medication use during brief structured interviews underwent detailed structured interviews with the Schedule for Affective Disorders and Schizophrenia. Diagnoses were based on the Research Diagnostic Criteria (RDC), and family history was determined with the Family History RDC. Of the 121 volunteers, 16.5% met criteria for diagnoses of current mental disorders. Of the 104 without current DSM-III axis I diagnoses, 35.6% had past histories and 39.4% had family histories of mental illness. These results emphasize the need for thorough assessment of "normal volunteers."
Uploads
Papers by J. Endicott