To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The dosimetric and clinical advantages offered by implementation of pencil beam scanning (PBS) proton therapy for moving thoracic tumours is hindered by interplay effect. The purpose of this study is to evaluate the impact of large proton beam spot size along with adaptive aperture (AA) and various motion mitigation techniques on the interplay effect for a range of motion amplitudes in a three-dimensional (3D) respiratory motion phantom.
Materials and Methods:
Point doses using ionisation chamber (IC) and planner dose distributions with radiochromic film were compared against the corresponding treatment planning system (TPS) information. A 3D respiratory motion phantom was scanned either for static or 4D computed tomographic (CT) technique for 6-, 10- and 14-mm motion amplitudes in SI direction. For free breathing (FB) treatment, a tumour was contoured on maximum intensity projection scan and an average scan was used for treatment planning. Each FB treatment was delivered with one, three and five volumetric repaintings (VRs). Three phases (CT40–60%) were extracted from the 4D-CT scans of each motion amplitude for the respiratory-gated treatment and were used for the treatment planning and delivery. All treatment plans were made using AA and robustly optimised with 5-mm set-up and 3·5% density uncertainty. A total of 26 treatment plans were delivered to IC and film using static, dynamic and respiratory-gated treatments combinations. A percent dose difference between IC and TPS for the point dose and gamma indices for film–TPS planner dose comparison was used.
The dose profile of film and TPS for the static phantom matched well, and percent dose difference between IC and TPS was 0·4%. The percent dose difference for all the gated treatments were below 3·0% except 14-mm motion amplitude-gated treatment. The gamma passing rate was more than 95% for film–TPS comparison for all gated treatment for the investigated gamma acceptance criteria. For FB treatments, the percent dose difference for 6-, 10- and 14-mm motion amplitude was 1·4%, −2·7% and −4·1%, respectively. As the number of VR increased, the percent difference between measured and calculated values decreased. The gamma passing rate met the required tolerance for different acceptance criteria except for the 14-mm motion amplitude FB treatment.
The PBS technique for the FB thoracic treatments up to 10-mm motion amplitude can be implemented with an acceptable accuracy using large proton beam spot size, AA and robust optimisation. The impact of the interplay effect can be reduced with VR and respiratory-gated treatment and extend the treatable tumour motion amplitude.
Cognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane, clinicaltrials.gov, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological, neurostimulation, or psychological interventions for bipolar disorder. Twenty-two trials were identified, evaluating a total of 16 different pro-cognitive interventions. The methodological quality of the identified trials were assessed using the Cochrane Risk of Bias tool. Currently, no intervention (i.e., pharmacologic, neurostimulation, cognitive remediation) has demonstrated robust and independent pro-cognitive effects in adults with bipolar disorder. Findings are preliminary and methodological limitations limit the interpretation of results. Methodological considerations including, but not limited to, the enrichment with populations with pre-treatment cognitive impairment, as well as the inclusion of individuals who are in remission are encouraged. Future trials may also consider targeting interventions to specific cognitive subgroups and the use of biomarkers of cognitive function.
Tracheostomy for coronavirus disease 2019 pneumonitis patients requiring prolonged invasive mechanical ventilation remains a matter of debate. This study analysed the timing and outcomes of percutaneous tracheostomy, and reports our experience of a dedicated ENT–anaesthetics department led tracheostomy team.
A prospective single-centre observational study was conducted of patients undergoing tracheostomy, who had been diagnosed with coronavirus disease 2019 pneumonitis, between 21st March and 20th May 2020.
Eighty-one patients underwent tracheostomy after a median (interquartile range) of 16 (13–20) days of invasive mechanical ventilation. Median follow-up duration was 32 (23–40) days. Of patients, 86.7 per cent were successfully liberated from invasive mechanical ventilation in a median (interquartile range) of 12 (7–16) days. Moreover, 68.7 per cent were subsequently discharged from hospital. On univariate analysis, there was no difference in outcomes between early (before day 14) and late (day 14 or later) tracheostomy. The mortality rate was 8.6 per cent and no deaths were tracheostomy related.
Outcomes appear favourable when patients are carefully selected. Percutaneous tracheostomy performed via a multidisciplinary approach, with appropriate training, was safe and optimised healthcare resource utilisation.
The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers.
In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes.
From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country.
A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries.
This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.
Inflammatory bowel disease (IBD) [i.e., Crohn’s disease (CD) and ulcerative colitis (UC)] has been considered a relative contraindication for radiation therapy (RT) to the abdomen or pelvis, potentially preventing patients with a diagnosis of IBD from receiving definitive therapy for their malignancy.
Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) conventions, a PubMed/MEDLINE literature search was conducted using the keywords RT, brachytherapy, inflammatory bowel disease, Crohn’s disease, ulcerative colitis and toxicity.
A total of 1,206 publications were screened with an addition of 8 studies identified through hand searching. Nineteen studies met the inclusion criteria for quantitative analysis. The total population across all studies was 497 patients, 50·5% having UC, 37% having CD and an additional 12·5% having unspecified IBD. Primary gastrointestinal malignancy (55%) followed by prostate cancer (40%) composed the bulk of the population. Acute and late grade 3 or greater gastrointestinal specific toxicity ranged from 0–23% to 0–13% respectively for those patients with IBD treated with RT to the abdomen or pelvis. In the literature reviewed, RT does not appear to increase fistula or stricture formation or IBD flares; however, one study did note RT to be a statistically significant risk factor for subsequent IBD flare on multivariate analysis.
A review of reported acute and late toxicities suggests that patients with IBD should still be considered for definitive radiotherapy. Patient characteristics including IBD distribution relative to the irradiated field, inflammatory activity at the time of radiation, overall disease severity and disease phenotype in the case of CD (fistulising versus stricturing versus inflammatory only) should be considered on an individual basis when evaluating potential patients. When possible, advanced techniques with strict organ at risk dose constraints should be employed to limit toxicity in this patient population.
Experiments were conducted to study in vitro maturation of prepubertal goat oocytes and their developmental potential after chemical activation. In Experiment 1, cumulus–oocytes complexes collected from the ovaries of prepubertal goats slaughtered at a local abattoir were matured in vitro in TCM-199-based medium supplemented with 10 µg/ml luteinizing hormone (LH) (treatment 1) or 10 µg/ml LH + 0.1 mM l-cysteine (treatment 2). In Experiment 2, mature oocytes were activated with either 5 µM ionomycin or 7% ethanol. After 18 h, some oocytes were randomly fixed and stained to evaluate their chromatin status, while others were cultured in embryo culture medium to study their further development. In Experiment 3, oocytes activated with 5 µM ionomycin were cultured for 7 days in one of the four different culture media [Charles Rosenkrans medium (CR-1), TCM-199, potassium simplex optimization medium (KSOM) and synthetic oviductal fluid (SOF)] to study their developmental potential. The maturation rate in control, treatment 1, and treatment 2 media did not differ from each other (P > 0.05). However, the lowest degeneration of oocytes was observed in treatment 3 (P < 0.05) when compared with the other two groups. The proportion of activated oocytes was higher, while non-activated oocytes were lower in ionomycin group when compared with the group activated with ethanol (P < 0.05). The proportions of oocytes cleaved were 65.7, 56.8, 61.0 and 54.4% in CR-1, TCM-199, KSOM and SOF medium, respectively, with no significant difference. However, further development of cleaved oocytes was better in KSOM followed by SOF.
This Research Reflection provides an overview of three interrelated topics: (i) lameness in dairy cows, demonstrating the underpinning importance of the condition, (ii) dairy farmer detection, diagnosis and treatment of lameness and associated foot lesions as well as dairy farmer perceptions towards the condition and (iii) lameness detection technologies, and their potential application on farm to automate the detection of lameness in commercial dairy herds. The presented literature clearly demonstrates that lameness is a major health issue in dairy herds, compromising dairy cow welfare and productivity, and resulting in significant economic implications for dairy farmers. Despite this, dairy farmers fail to perceive lameness as a serious threat to their dairy business. This restricted perception of the importance of lameness may be a product of limited ability to detect lame cows. Many automated lameness detection technologies have been proposed to assist dairy farmers in managing their herds. However, limitations such as cost, performance and dairy farmer perception of the usefulness of these technologies, has lead to poor uptake. It can, therefore, be concluded that there is a need to more thoroughly evaluate the effectiveness of these technologies under on-farm conditions, potentially in the form of a demonstration farm network. This will allow generation of the necessary data required to show dairy farmers that these technologies are reliable and are economically rational for their dairy business.
A household-level constant visual deterrent advocacy campaign to reduce tobacco intake was conducted in rural Bangladesh.
To evaluate smoking tobacco expenditure by campaign components.
We conducted a single-blind clustered randomized controlled trial on 630 adult male household heads from 16 chars (riverine islands) in rural northern Bangladesh, between November 2018 and January 2019. Intervention allotment was randomized at the char level to minimize spillovers, with 8 chars in treatment and control groups each. The intervention provided households in treatment chars (n = 323) with two visual warning posters, detailing the health effects of tobacco on oneself and external actors, to be hung inside the household for 4 weeks. Households in control chars (n = 307) received nothing. Reported daily smoking (log) tobacco expenditure values were the primary outcome of interest.
Final analysis was conducted using 251 and 210 smokers in treatment and control chars respectively. The intervention reduced relative smoking tobacco expenditure by 12.8% (95% CI −31.45 to 5.81) but was not statistically significant (P-value = 0.163). Weak to moderate emotional reactions to the posters was identified as a reason for the statistical insignificance.
For a visual anti-tobacco intervention to have a substantial impact, it must induce strong emotional responses.
Parthenium weed is an invasive species in a growing number of countries where it infests numerous crop fields, including sorghum. Two field studies were conducted to quantify the effect of parthenium weed on the performance of grain sorghum at different weed densities (0, 5, 10, 15 and 20 plants m−2) and durations of weed-crop competition (season-long weed-free, weed-free after 2, 4, 6 or 8 weeks, and season-long weedy). Our aim was to identify the density threshold and ideal duration to control parthenium weed in sorghum fields. Both field experiments were planned in a randomised complete block design each with three replications in 2016 and were repeated in 2017. Parthenium weed biomass increased significantly with increasing density and competition duration. The increasing parthenium weed density had a linear negative effect on sorghum growth, yield and yield-contributing traits. The highest yield loss, of up to 66%, was recorded at the highest parthenium weed density of 20 plants m−2 when compared to weed-free treatment. In addition, the season-long competition of this weed with sorghum caused 81% reduction in grain yield over weed-free treatment. According to our results, parthenium weed should be managed below a density of 5 plants m−2 and throughout the crop growth duration in grain sorghum fields as it can cause serious yield losses even at low densities and through strong competition at early as well as late growth stages of the crop.
This study aims to assess the impact of a behavioural intervention, in the form of a self-monitoring record-keeping logbook, in reducing smoking tobacco expenditure amongst adult male household heads in rural Bangladesh.
The experiment was designed as a single-blind clustered randomised controlled trial utilising two-stage random sampling. A total of 650 adult male household heads were sampled from 16 chars (riverine islands) from Gaibandha, Northern Bangladesh, with eight chars in treatment and control groups each, between November 2018 and January 2019. The intervention consisted of a logbook to record daily smoking tobacco intake for 4 weeks provided only to participants in treatment chars (n = 332) while households in control chars received nothing (n = 318).
Final analysis was conducted using 222 and 210 households in the treatment and control chars respectively. The logbook intervention had a significant impact (P-value = 0.040) on reducing daily tobacco expenditure by 14% (α = 95%; CI: −0.273, −0.008) for the treatment group relative to the control group based on a difference-in-difference estimator. This is equivalent to a reduction of 20 cigarettes or 140 bidis smoked in a month.
Our minimal contact intervention successfully induced a reduction in smoking tobacco expenditure, which could effectively be incorporated with existing programs in the char regions of Bangladesh.
Cold dissection is the most commonly used tonsillectomy technique, with low post-operative haemorrhage rates. Coblation is an alternative technique that may cause less pain, but could have higher post-operative haemorrhage rates.
This study evaluated the peri-operative outcomes in paediatric tonsillectomy patients by comparing coblation and cold dissection techniques.
A systematic review was conducted of all comparative studies of paediatric coblation and cold dissection tonsillectomy, up to December 2018. Any studies with adults were excluded. Outcomes such as pain, operative time, and intra-operative, primary and secondary haemorrhages were recorded.
Seven studies contributed to the summative outcome. Coblation tonsillectomy appeared to result in less pain, less intra-operative blood loss (p < 0.01) and a shorter operative time (p < 0.01). There was no significant difference between the two groups for post-operative haemorrhage (p > 0.05).
The coblation tonsillectomy technique may offer better peri-operative outcomes when compared to cold dissection, and should therefore be offered in paediatric cases, before cold dissection tonsillectomy.
Simultaneous PET/MR/EEG (Positron Emission Tomography – Magnetic Resonance – Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm.
It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.
The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.
Semiconducting nanostructures such as nanowires (NWs) have been used as building blocks for various types of sensors, energy storage and generation devices, electronic devices and for new manufacturing methods involving printed NWs. The response of these sensing/energy/electronic components and the new fabrication methods depends very much on the quality of NWs and for this reason it is important to understand the growth mechanism of 1D semiconducting nanostructures. This is also important to understand the compatibility of NW growth steps and tools used in the process with these unconventional substrates such as plastic that are used in flexible and large area electronics. Therefore, this Element presents at length discussion about the growth mechanisms, growth conditions and the tools used for the synthesis of NWs. Although NWs from Si, ZnO and carbon nanotubes (CNTs) are included, the discussion is generic and relevant to several other types of NWs as well as heterostructures.
There is a scarcity of specialist trainers and supervisors for psychosocial interventions in low- and middle-income countries. A cascaded model of training and supervision was developed to sustain delivery of an evidence-based peer-delivered intervention for perinatal depression (the Thinking Healthy Programme) in rural Pakistan. The study aimed to evaluate the model.
Mixed methods were employed as part of a randomised controlled trial of the intervention. Quantitative data consisted of the peers' competencies assessed during field training and over the implementation phase of the intervention, using a specially developed checklist. Qualitative data were collected from peers and their trainers through 11 focus groups during the second and third year of intervention rollout.
Following training, 43 peers out of 45 (95%) achieved at least a ‘satisfactory’ level of competency (scores of ⩾70% on the Quality and Competency Checklist). Of the cohort of 45 peers initially recruited 34 (75%) were retained over 3 years and showed sustained or improved competencies over time. Qualitatively, the key factors contributing to peers' competency were use of interactive training and supervision techniques, the trainer–peer relationship, and their cultural similarity. The partnership with community health workers and use of primary health care facilities for training and supervision gave credibility to the peers in the community.
The study demonstrates that lay-workers such as peers can be trained and supervised to deliver a psychological intervention using a cascaded model, thus addressing the barrier of scarcity of specialist trainers and supervisors.
A core question in the debate about how to organise mental healthcare is whether in- and out-patient treatment should be provided by the same (personal continuity) or different psychiatrists (specialisation). The controversial debate drives costly organisational changes in several European countries, which have gone in opposing directions. The existing evidence is based on small and low-quality studies which tend to favour whatever the new experimental organisation is.
We compared 1-year clinical outcomes of personal continuity and specialisation in routine care in a large scale study across five European countries.
This is a 1-year prospective natural experiment conducted in Belgium, England, Germany, Italy and Poland. In all these countries, both personal continuity and specialisation exist in routine care. Eligible patients were admitted for psychiatric in-patient treatment (18 years of age), and clinically diagnosed with a psychotic, mood or anxiety/somatisation disorder.
Outcomes were assessed 1 year after the index admission. The primary outcome was re-hospitalisation and analysed for the full sample and subgroups defined by country, and different socio-demographic and clinical criteria. Secondary outcomes were total number of inpatient days, involuntary re-admissions, adverse events and patients’ social situation. Outcomes were compared through mixed regression models in intention-to-treat analyses. The study is registered (ISRCTN40256812).
We consecutively recruited 7302 patients; 6369 (87.2%) were followed-up. No statistically significant differences were found in re-hospitalisation, neither overall (adjusted percentages: 38.9% in personal continuity, 37.1% in specialisation; odds ratio = 1.08; confidence interval 0.94–1.25; p = 0.28) nor for any of the considered subgroups. There were no significant differences in any of the secondary outcomes.
Whether the same or different psychiatrists provide in- and out-patient treatment appears to have no substantial impact on patient outcomes over a 1-year period. Initiatives to improve long-term outcomes of psychiatric patients may focus on aspects other than the organisation of personal continuity v. specialisation.
Accurate three-dimensional dosimetry is essential in modern radiotherapy techniques such as volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). In this research work, the PRESAGE® dosimeter was used as quality assurance (QA) tool for VMAT planning for head and neck (H&N) cancer.
Material and method
Computer tomography (CT) scans of an Image Radiation Oncology Core (IROC) H&N anthropomorphic phantom with both IROC standard insert and PRESAGE® insert were acquired separately. Both CT scans were imported into the Pinnacle (9.4 version) TPS for treatment planning, where the structures [planning target volume (PTV), organs at risk) and thermoluminescent detectors (TLDs) were manually contoured and used to optimise a VMAT plan. Treatment planning was done using VMAT (dual arc: 182°–178°, 178°–182°). Beam profile comparisons and gamma analysis were used to quantify agreement with film, PRESAGE® measurement and treatment planning system (TPS) calculated dose distribution.
The average ratio of TLD measured to calculated doses at the four PTV locations in the H&N phantom were between 0·95 to 0·99 for all three VMAT deliveries. Dose profiles were taken along the left–right, the anterior–posterior and superior–inferior axes, and good agreement was found between the PRESAGE® and Pinnacle profile. The mean value of gamma results for three VMAT deliveries in axial and sagittal planes were found to be 94·24 and 93·16% when compared with film and Pinnacle, respectively. The average values comparing the PRESAGE® results and dose values calculated on Pinnacle were observed to be 95·29 and 94·38% in the said planes, respectively, using a 5%/3 mm gamma criteria.
The PRESAGE® dose measurements and calculated dose of pinnacle show reasonable agreement in both axial and sagittal planes for complex dual arc VMAT treatment plans. In general, the PRESAGE® dosimeter is found to be a feasible QA tool of VMAT plan for H&N cancer treatment.
UK guidelines recommend routine HIV testing in high prevalence emergency departments (ED) and targeted testing for HBV and HCV. The ‘Going Viral’ campaign implemented opt-out blood-borne virus (BBV) testing in adults in a high prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current engagement in care, and severity of disease was established. LTC was defined as patient informed plus ⩾1 clinic visit. A total of 6211/24 981 ED attendees were tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%) required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged). 16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients requiring LTC had advanced disease (CD4 <350, APRI (AST-to-Platelet Ratio Index) >1, Fibroscan F3/F4 or liver cancer), including five with AIDS-defining conditions and three hepatocellular carcinomas. There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV patients. ED testing was valuable as one-third of those requiring LTC (new, disengaged or unknown status patients) had advanced disease.