Association between psychological distress trajectories from adolescence to midlife and mental health during the pandemic: evidence from two British birth cohorts.

BACKGROUND: This paper examined whether distinct life-course trajectories of psychological distress from adolescence to midlife were associated with poorer mental health outcomes during the pandemic. METHODS: We present a secondary analysis of two nationally representative British birth cohorts, the 1958 National Child Development Study (NCDS) and 1970 British Cohort Study (BCS70). We used latent variable mixture models to identify pre-pandemic longitudinal trajectories of psychological distress and a modified Poisson model with robust standard errors to estimate associations with psychological distress, life satisfaction and loneliness at different points during the pandemic. RESULTS: Our analysis identified five distinct pre-pandemic trajectories of psychological distress in both cohorts. All trajectories with prior symptoms of psychological distress irrespective of age of onset, severity and chronicity were associated with a greater relative risk of poorer mental health outcomes during the pandemic and the probability of poorer mental health associated with psychological distress trajectories remained fairly constant. The relationship was not fully attenuated when most recent pre-pandemic psychological distress and other midlife factors were controlled for. CONCLUSIONS: Whilst life-course trajectories with any prior symptoms of psychological distress put individuals at greater risk of poor mental health outcomes during the pandemic, those with chronic and more recent occurrences were at highest risk. In addition, prior poor mental health during the adult life-course may mean individuals are less resilient to shocks, such as pandemics. Our findings show the importance of considering heterogeneous mental health trajectories across the life-course in the general population in addition to population average trends.

Sensor Noise in LISA Pathfinder: In-Flight Performance of the Optical Test Mass Readout.

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data.

LISA Pathfinder Performance Confirmed in an Open-Loop Configuration: Results from the Free-Fall Actuation Mode.

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

Beyond the Required LISA Free-Fall Performance: New LISA Pathfinder Results down to 20 µHz.

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 µHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10 fm s^{-2}/sqrt[Hz] at 20 µHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

Longitudinal associations between television in the bedroom and body fatness in a UK cohort study.

OBJECTIVE: To assess longitudinal associations between screen-based media use (television (TV) and computer hours, having a TV in the bedroom) and body fatness among UK children. METHODS: Participants were 12 556 children from the UK Millennium Cohort Study who were followed from age 7 to age 11 years. Associations were assessed between screen-based media use and the following outcomes: body mass index (BMI), fat mass index (FMI), and overweight. RESULTS: In fully adjusted models, having a bedroom TV at age 7 years was associated with significantly higher BMI and FMI (excess BMI for boys=0.29, 95% confidence interval (CI) 0.06-0.52; excess BMI for girls=0.57, 95% CI 0.31-0.84; excess FMI for boys=0.20, 95% CI 0.04-0.37; excess FMI for girls=0.39, 95% CI 0.21-0.57) and increased risk of being overweight (relative risk (RR) for boys=1.21, 95% CI 1.07-1.36; RR for girls=1.31, 95% CI 1.15-1.48) at age 11 years, compared with having no bedroom TV. Hours spent watching TV or digital versatile disks were associated with increased risk of overweight among girls only. Computer use at age 7 years was not related to later body fatness for either gender. CONCLUSION: Having a TV in the child's bedroom was an independent risk factor for overweight and increased body fatness in this nationally representative sample of UK children. Childhood obesity prevention strategies should consider TVs in children's bedrooms as a risk factor for obesity.

Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA Pathfinder.

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

Sub-Femto-g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results.

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

The impact of caring for an adult with intellectual disability and psychiatric comorbidity on carer stress and psychological distress.

BACKGROUND: Given that carers of individuals with intellectual disability (ID) and carers of individuals with psychiatric disorders experience elevated levels of stress and psychological distress, carers of individuals with both ID and a comorbid psychiatric disorder are potentially at even greater risk for psychological difficulties. The aim of the present study was to investigate the psychological well-being of carers of adults with a dual diagnosis compared with carers of adults with intellectual disability alone. METHOD: Four-hundred and forty-two questionnaires were sent to four community services and seventy-five family carers of adults with intellectual disability responded. Psychological well-being of carers was assessed using the Questionnaire on Resources and Stress - Friedrich edition (QRS-F) and the General Health Questionnaire (GHQ). Comorbid psychopathology for their family member with ID was assessed using the Reiss Screen for Maladaptive Behaviour (RSMB). RESULTS: Twenty-four percent of the individuals with ID were reported to have comorbid psychopathology. Between-group analyses compared carers of people with ID and comorbid psychopathology to carers of people with ID alone. Regression analyses examined the relationship between psychopathology and other care-related variables to carer stress and psychological distress. Carers of people with ID and comorbid psychopathology were found to have significantly higher levels of stress and psychological distress than carers of people with ID alone. Autism was found to be the only significant predictor of both stress and psychological distress among measures of psychopathology. CONCLUSIONS: Additional comorbid psychopathology in individuals with intellectual disability has a significant impact on their carers' psychological well-being.

A review of the data quality and comparability of case-control studies of low-level exposure to benzene in the petroleum industry.

PURPOSE: Published case-control studies of risks of leukaemia following low exposures to benzene in the distribution of petroleum (gasoline) have not all identified the same level of risk, but the studies have had differences in cohort inclusion, case determination and availability of occupational and lifestyle data. We reviewed the quality and comparability of the data from three (of four) studies. METHODS: Through site visits, discussions with the investigators and reading study reports, we reviewed and audited the methods used for selecting cases and controls, for estimating individual exposures and for analysing and interpreting the data. Case-control comparisons of exposures were examined using customized graphs. RESULTS: We found that there were no issues of subject selection, methods or general data quality that were likely to have distorted their internal comparisons; we could not check in detail whether the metric for exposure assessments was the same across the studies; the exposure assessments for the Australian study required the least backward estimation, and the Canadian, which also had fewest cases, the most; evidence of an increased risk at higher exposures in Australia was convincing. CONCLUSIONS: The findings are consistent with some effect of benzene at higher lifetime exposures. A proposed pooled analysis should improve quantification of any exposure-response relationship.

Cancer waiting times: what is the value of a lymphoma waiting time?

BACKGROUND AND AIM: Waiting times for patients with lymphoma have been reported across the United Kingdom since 2005. Lymphoma however, is not a single disease but a wide spectrum of lymphoid tumours that range from the most malignant to the most indolent, from highly curable to incurable. We now question the value of the current system that reports lymphoma waiting time on a quarterly basis and makes no allowance for the different types of lymphoma. METHOD: Four hundred and sixty nine cases of lymphoma were registered in the west of Scotland in 2004. Complete datasets were available on 428. Patient demographic data, subtypes of lymphoma, biopsy site and referral urgency data were linked to the waiting times analysis for 2004 for the three subtypes, Lymphoma (HL), Diffuse Large B Cell (DLBC) and follicular Non Hodgkin Lymp (NHL). RESULTS: Patients with HL were younger, more likely to receive urgent referral and have a diagnosis made from neck node biopsy than the other two groups. Patients with DLBC NHL however had the shortest interval between presentation and the start of treatment and were subsequently more likely to receive treatment within 62 days than patients with either follicular NHL (p < 0.001) or HL (p < 0.05). CONCLUSION: Lymphoma subtype is a major factor determining the rate of progress from presentation to the start of treatment, hence the waiting time.

Cervical lymphadenopathy resulting in a diagnosis of lymphoma.

BACKGROUND AND AIMS: Currently there is no protocol in the west of Scotland for the investigation of a patient with a lymph node in the neck which might contain lymphoma. The aim of this audit was to examine the current management of these patients. METHODS: Data were collected on 112 patients diagnosed as having lymphoma from a neck node biopsy within a 12 month period from 1st November 2004 to 31st October 2005. Biopsy data were collected in combination with the first point of consultation, investigations used to arrive at diagnosis and any associated complications. RESULTS: Eighty seven percent of patients underwent excision biopsy with complications noted in 7%. Fine needle aspiration cytology (FNAC) was carried out in 60% of which 34% were ultrasound guided. Core biopsy was carried out in 17% of which 63% were ultrasound guided, Forty-five percent of patients were first referred to ear, nose and throat (ENT) surgery, 17% to general surgery, 14% to haematology, 13% to general medicine and 11% to other specialties. CONCLUSION: This audit shows that there was a wide range of first points of consultation and diagnostic procedures used. It is recommended that there should be access for all patients with cervical lymphadenopathy to a weekly neck lump clinic with standardised protocols for lymphoma diagnosis. This should ensure that patients are diagnosed accurately and treated in a timely manner.

Person Focused Training: a model for delivering positive behavioural supports to people with challenging behaviours.

BACKGROUND: Person Focused Training is introduced as a model of service delivery for people with severe challenging behaviours. It is defined as training and supporting staff to conduct functional assessments and to design and implement positive behavioural support for specific individuals with challenging behaviours. METHOD: Longitudinal outcome data are presented from 138 behaviour support plans developed by staff over a seven year period were analysed to determine reductions in frequency of challenging behaviours. Degree of behaviour change was determined across topography of behaviour, gender, age, level of disability, location of residence and role of course participant. RESULTS: Results indicate that the implementation by staff of behaviour support plans are associated with significant improvement in 77% of cases at an average follow-up of 22 months after implementation of support plans. Only location of residence was identified as related to reduction in challenging behaviours with large residential centres being associated with lower rates of behavioural improvement. CONCLUSIONS: It is argued that Person Focused training may represent an alternative to existing models of supporting individuals with challenging behaviours. The implications of front-line staff designing and implementing behaviour support plans for the organisation of services and the role of the clinical psychologist are considered.

Inappropriate antidiuretic hormone secretion, abdominal pain and disseminated varicella-zoster virus infection: an unusual and fatal triad in a patient 13 months post Rituximab and autologous stem cell transplantation.

We report a case of varicella-zoster virus (VZV) infection associated with severe abdominal pain, inappropriate antidiuretic hormone (ADH) secretion (SIADH) and death, 13 months post-autologous peripheral blood stem cell transplantation (PBSCT). This unusual clinical triad has been reported twice in the setting of allogeneic bone marrow transplantation, however it has not been reported after autologous transplantation and never so long after transplantation. We speculate as to why this occurred, as early recognition might have altered the clinical outcome.

Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation.

The human protein ABC7 belongs to the adenosine triphosphate-binding cassette transporter superfamily, and its yeast orthologue, Atm1p, plays a central role in the maturation of cytosolic iron-sulfur (Fe/S) cluster-containing proteins. Previously, a missense mutation in the human ABC7 gene was shown to be the defect in members of a family affected with X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A). Here, the promoter region and the intron/exon structure of the human ABC7 gene were characterized, and the function of wild-type and mutant ABC7 in cytosolic Fe/S protein maturation was analyzed. The gene contains 16 exons, all with intron/exon boundaries following the AG/GT rule. A single missense mutation was found in exon 10 of the ABC7 gene in 2 affected brothers with XLSA/A. The mutation was a G-to-A transition at nucleotide 1305 of the full-length cDNA, resulting in a charge inversion caused by the substitution of lysine for glutamate at residue 433 C-terminal to the putative sixth transmembrane domain of ABC7. Expression of normal ABC7 almost fully complemented the defect in the maturation of cytosolic Fe/S proteins in a yeast strain in which the ATM1 gene had been deleted (Deltaatm1 cells). Thus, ABC7 is a functional orthologue of Atm1p. In contrast, the expression of mutated ABC7 (E433K) or Atm1p (D398K) proteins in Deltaatm1 cells led to a low efficiency of cytosolic Fe/S protein maturation. These data demonstrate that both the molecular defect in XLSA/A and the impaired maturation of a cytosolic Fe/S protein result from an ABC7 mutation in the reported family.

Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.

X-linked sideroblastic anemia (XLSA) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo XLSA mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated XLSA hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two XLSA probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia.

Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature.

Lymphomas account for 2-5% of all oral malignancies and are the third most common in this site. This case report appears to be the first in the world literature describing spontaneous regression in the oral cavity of a subset of non-Hodgkins lymphomas known as Ki-1 anaplastic large cell lymphomas (ALCL). Ki-1 ALCL account for 2-7% of all non-Hodgkins lymphomas and the clinical presentation is variable; they may arise de novo or in the setting of a separate primary lymphoma and commonly present in the extra-nodal location. Disease severity is also variable with waxing and waning lesions at one extreme which may spontaneously regress to bone marrow involvement in around 12% of cases. This case is especially interesting since the patient is a farmer, given the recent evidence that there may be a link between non-Hodgkins lymphoma and this occupation.

Severe vincristine toxicity in combination with itraconazole.

We report two patients with acute lymphoblastic leukaemia (ALL) who were entered into the current MRC adult ALL trial (UKALL XII) in whom unusually severe vincristine induced neurotoxicity developed. This appeared to be the result of an interaction with itraconazole suspension.

Malignant and corticosteroid-dependent idiopathic anaphylaxis: successful responses to ketotifen.

BACKGROUND: Malignant idiopathic anaphylaxis refers to the most severe form of idiopathic anaphylaxis where defined episodes of idiopathic anaphylaxis are not controlled when the prednisone is reduced below at least 60 mg every other day or 20 mg daily. Corticosteroid-dependent idiopathic anaphylaxis refers to patients with idiopathic anaphylaxis who require continuous daily or alternate day prednisone at threshold doses for control of idiopathic anaphylaxis. Ketotifen has been reported to help induce remission in some patients with idiopathic anaphylaxis and has steroid sparing effects in other patients with idiopathic anaphylaxis. METHODS: We present five patients, two with malignant idiopathic anaphylaxis and three with corticosteroid-dependent idiopathic anaphylaxis, who responded to the administration of ketotifen. RESULTS: All five patients, while receiving ketotifen, had a reduction or resolution of their episodes of idiopathic anaphylaxis and prednisone was tapered and discontinued. CONCLUSION: Ketotifen is shown to be successful in inducing remission in two patients with malignant idiopathic anaphylaxis and in three additional patients with corticosteroid-dependent idiopathic anaphylaxis. An additional patient with malignant idiopathic anaphylaxis had prednisone stopped after elective hip surgery.