Postgraduate study can be mentally, physically and emotionally challenging. The levels of anxiety and depression in postgraduate students are much higher than those in the general population, and ...isolation can also be a problem, especially for students who are marginalised due to gender, race, sexuality, disability or being a first-generation and/or international student. These challenges are not new, but awareness of them has increased over the past decade, as have efforts by institutions to make students feel supported. Under the umbrella of a Doctoral Training Partnership, we developed a programme in which reflective practice is employed to help postgraduate students navigate work environments, deal with difficult supervisory or professional relationships, and improve their work-life balance. Additionally, this reflective practice is allowing the training partnership to tailor support to its students, enabling them to effectively nurture our next generation of bioscientists.
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a ...sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin.
Aims
This study aims to assess the feasibility of an randomized controlled trial (RCT) to test treatment efficacy of acupuncture for symptoms of overactive bladder syndrome (OAB), a common long‐term ...condition with physical, psychological, social and sexual consequences.
Methods
A total of 30 participants were recruited and randomized to either standard conservative management for OAB or standard conservative management plus acupuncture. Standard care consisted of individually tailored advice regarding bladder health, pelvic floor exercises and lifestyle adjustments. The intervention group received 6 sessions of acupuncture over an 8‐week period. Outcomes measured included adherence to the study protocol, recruitment rate, participant attrition rate and adverse events. A 3‐day bladder diary and Incontinence Questionnaire—short form questionnaire were used to assess symptoms. The ICEpop CAPability measure for Adults measure was used to assess well‐being. Outcomes were collected at baseline, after 8 weeks of intervention and 6 weeks after completing intervention. An exit questionnaire captured participant experience data.
Results
Comparison of the two groups at baseline did not detect statistically significant differences in demographics and symptom profile. A total of 23 participants completed all study proceedures. Recruitment was completed in 11 months, quicker than anticipated. No serious adverse events occurred; minor adverse events were recorded in 11/114 (9.6%) treatments. A total of seven participants failed to complete one or more study proceedures with an overall attrition rate of 23.3%.
Conclusions
Most participants completed all aspects of the study and found the protocol acceptable. The interventions appear safe and well tolerated. The concept of a large‐scale RCT with a similar protocol was proven and appears feasible based on this pilot work.
Background
Overactive bladder is a common, long‐term symptom complex, which includes frequency of micturition, urgency with or without associated incontinence and nocturia. Around 11% of the ...population have symptoms, with this figure increasing with age. Symptoms can be linked to social anxiety and adaptive behavioural change. The cost of treating overactive bladder is considerable, with current treatments varying in effectiveness and being associated with side effects. Acupuncture has been suggested as an alternative treatment.
Objectives
To assess the effects of acupuncture for treating overactive bladder in adults, and to summarise the principal findings of relevant economic evaluations.
Search methods
We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (including In‐Process, Epub Ahead of Print, Daily), ClinicalTrials.gov and WHO ICTRP (searched 14 May 2022). We also searched the Allied and Complementary Medicine database (AMED) and bibliographic databases where knowledge of the Chinese language was necessary: China National Knowledge Infrastructure (CNKI); Chinese Science and Technology Periodical Database (VIP) and WANFANG (China Online Journals), as well as the reference lists of relevant articles.
Selection criteria
We included randomised controlled trials (RCTs), quasi‐RCTs and cross‐over RCTs assessing the effects of acupuncture for treating overactive bladder in adults.
Data collection and analysis
Four review authors formed pairs to assess study eligibility and extract data. Both pairs used Covidence software to perform screening and data extraction. We assessed risk of bias using Cochrane's risk of bias tool and assessed heterogeneity using the Chi2 testand I2 statistic generated within the meta‐analyses. We used a fixed‐effect model within the meta‐analyses unless there was a moderate or high level of heterogeneity, where we employed a random‐effects model. We used the GRADE approach to assess the certainty of evidence.
Main results
We included 15 studies involving 1395 participants in this review (14 RCTs and one quasi‐RCT). All included studies raised some concerns regarding risk of bias. Blinding of participants to treatment group was only achieved in 20% of studies, we considered blinding of outcome assessors and allocation concealment to be low risk in only 25% of the studies, and random sequence generation to be either unclear or high risk in more than 50% of the studies.
Acupuncture versus no treatment
One study compared acupuncture to no treatment. The evidence is very uncertain regarding the effect of acupuncture compared to no treatment in curing or improving overactive bladder symptoms and on the number of minor adverse events (both very low‐certainty evidence). The study report explicitly stated that no major adverse events occurred. The study did not report on the presence or absence of urinary urgency, episodes of urinary incontinence, daytime urinary frequency or episodes of nocturia.
Acupuncture versus sham acupuncture
Five studies compared acupuncture with sham acupuncture. The evidence is very uncertain about the effect of acupuncture on curing or improving overactive bladder symptoms compared to sham acupuncture (standardised mean difference (SMD) ‐0.36, 95% confidence interval (CI) ‐1.03 to 0.31; 3 studies; 151 participants; I2 = 65%; very low‐certainty evidence). All five studies explicitly stated that there were no major adverse events observed during the study. Moderate‐certainty evidence suggests that acupuncture probably makes no difference to the incidence of minor adverse events compared to sham acupuncture (risk ratio (RR) 1.28, 95% CI 0.30 to 5.36; 4 studies; 222 participants; I² = 0%). Only one small study reported data for the presence or absence of urgency and for episodes of nocturia. The evidence is of very low certainty for both of these outcomes and in both cases the lower confidence interval is implausible. Moderate‐certainty evidence suggests there is probably little or no difference in episodes of urinary incontinence between acupuncture and sham acupuncture (mean difference (MD) 0.55, 95% CI ‐1.51 to 2.60; 2 studies; 121 participants; I2 = 57%). Two studies recorded data regarding daytime urinary frequency but we could not combine them in a meta‐analysis due to differences in methodologies (very low‐certainty evidence).
Acupuncture versus medication
Eleven studies compared acupuncture with medication. Low‐certainty evidence suggests that acupuncture may slightly increase how many people's overactive bladder symptoms are cured or improved compared to medication (RR 1.25, 95% CI 1.10 to 1.43; 5 studies; 258 participants; I2 = 19%). Low‐certainty evidence suggests that acupuncture may reduce the incidence of minor adverse events when compared to medication (RR 0.34, 95% CI 0.26 to 0.45; 8 studies; 1004 participants; I² = 51%). The evidence is uncertain regarding the effect of acupuncture on the presence or absence of urinary urgency (MD ‐0.40, 95% CI ‐0.56 to ‐0.24; 2 studies; 80 participants; I2 = 0%; very low‐certainty evidence) and episodes of urinary incontinence (MD ‐0.33, 95% CI ‐2.75 to 2.09; 1 study; 20 participants; very low‐certainty evidence) compared to medication. Low‐certainty evidence suggests there may be little to no effect of acupuncture compared to medication in terms of daytime urinary frequency (MD 0.73, 95% CI ‐0.39 to 1.85; 4 studies; 360 participants; I2 = 28%). Acupuncture may slightly reduce the number of nocturia episodes compared to medication (MD ‐0.50, 95% CI ‐0.65 to ‐0.36; 2 studies; 80 participants; I2 = 0%, low‐certainty evidence).
There were no incidences of major adverse events in any of the included studies. However, major adverse events are rare in acupuncture trials and the numbers included in this review may be insufficient to detect these events.
Authors' conclusions
The evidence is very uncertain about the effect acupuncture has on cure or improvement of overactive bladder symptoms compared to no treatment. It is uncertain if there is any difference between acupuncture and sham acupuncture in cure or improvement of overactive bladder symptoms. This review provides low‐certainty evidence that acupuncture may result in a slight increase in cure or improvement of overactive bladder symptoms when compared with medication and may reduce the incidence of minor adverse events.
These conclusions must remain tentative until the completion of larger, higher‐quality studies that use relevant, comparable outcomes. Timing and frequency of treatment, point selection, application and long‐term follow‐up are other areas relevant for research.
Overactive bladder (OAB) affects around 12% of the adult population and is the subject of thousands of studies. Qualitative studies of OAB are less common and the patient voice is rarely heard. This ...protocol outlines the theoretical framework underpinning the study and defines the methodology that will be used to investigate the lived experience of OAB and choices regarding treatment options. This study will reference the patient experience of receiving acupuncture for OAB symptoms, a novel treatment with a growing evidence base. This is the first study to address patient experience related to acupuncture for OAB and may produce information of use to people with OAB, clinicians and those developing new pathways of care.
Display omitted
•Lived experience of overactive bladder symptoms.•Use of acupuncture as a treatment modality.•Qualitative investigation of treatment choices.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effects of acupuncture for treating OAB in adults; and summarise the principal findings of ...relevant economic evaluations.
Overactive bladder (OAB) is a common complaint, 1 in 9 of the adult population in the UK have symptoms. Three key symptoms lead to diagnosis, urinary urgency, frequency and nocturia, often ...accompanied by urinary incontinence. OAB has a profound effect on quality of life and is linked with anxiety and depression. OAB is under-diagnosed, treatments have known side effects, and some are invasive and costly. Acupuncture has been suggested as an alternative treatment and some evidence supports its further investigation. Limited work has been conducted in the UK and there is a dearth of patient experience studies worldwide. This thesis addresses the knowledge gap utilising a mixed methods research model based on the Medical Research Council’s framework for complex interventions. It consists of a comprehensive review of the pathophysiology of OAB and treatment strategies; a Cochrane Interventional Review of acupuncture to treat OAB; a feasibility study to test the delivery, safety and acceptability of acupuncture; and a qualitative study investigating patient’s experiences of having acupuncture for their symptoms. Possible causes of OAB are likely to be individual and multi-faceted. The Cochrane Review provided low certainty evidence that acupuncture may be more effective than medication for OAB, with a lower adverse event profile. However, the risk of bias in studies was high. There was no evidence found regarding the cost effectiveness of acupuncture for OAB. Feasibility of delivering acupuncture in a secondary care NHS setting was demonstrated, but the patient experience information collected lacked detail. The qualitative interview study rectified this gap. The themes developed demonstrated the profound effects of OAB on life experience and were overwhelmingly supportive of the use of acupuncture.
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a ...sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-AS.sup.r OXALI.sup.4000). SK-N-AS.sup.r OXALI.sup.4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-AS.sup.r OXALI.sup.4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-AS.sup.r OXALI.sup.4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-AS.sup.r OXALI.sup.4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-AS.sup.r OXALI.sup.4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-AS.sup.r OXALI.sup.4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin.
Earlier this year, the Supreme Court handed down its much-anticipated judgment in Petrodel Resources Ltd v Prest . The case raised important issues regarding the scope of section 24 of the ...Matrimonial Causes Act 1973, the doctrine of piercing the corporate veil and the law of resulting trusts. The decision had the potential radically to change the legal landscape for family practitioners, company practitioners, or both. This article considers where the law stands following this landmark decision and reflects on its ramifications for future cases.
Sexual reproduction often declines towards range edges, reducing fitness, dispersal and adaptive potential. For plants, sexual reproduction is frequently limited by inadequate pollination. While case ...studies show that pollen limitation can limit plant distributions, the extent to which pollination commonly declines towards plant range edges is unknown. Here, we use global databases of pollen-supplementation experiments and plant occurrence data to test whether pollen limitation increases towards plant range edges, using a phylogenetically controlled meta-analysis. While there was significant pollen limitation across studies, we found little evidence that pollen limitation increases towards plant range edges. Pollen limitation was not stronger towards the tropics, nor at species' equatorward versus poleward range limits. Meta-analysis results are consistent with results from targeted experiments, in which pollen limitation increased significantly towards only 14% of 14 plant range edges, suggesting that pollination contributes to range limits less often than do other interactions. Together, these results suggest pollination is one of the rich variety of potential ecological factors that can contribute to range limits, rather than a generally important constraint on plant distributions. This article is part of the theme issue 'Species' ranges in the face of changing environments (part I)'.
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