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Introduction Colorectal liver metastases (CRLM) are associated with a high recurrence rate after surgery. There is paucity of high-quality evidence regarding the nature and overall benefit of surveillance after hepatectomy for CRLM. As part of a broader programme of research, this study aimed to assess current strategies for surveillance after liver resection for CRLM and outline surgeons’ opinions regarding the benefit of postoperative surveillance. Methods An online survey was sent to clinicians performing surgery for CRLM at tertiary hepatobiliary centres in the UK. Results There were responses from a total of 23 centres (88% response rate); 15/23 centres used standardised surveillance protocols for all patients. Most centres followed patients up at six months, but there is variation in postoperative surveillance at 3, 9, 18 and beyond 60 months. Patient comorbidities, indeterminate findings on imaging, margin status and assessment of recurrence risk were identified as the major factors influencing personalised surveillance strategies. There was clear clinician equipoise regarding the costs and benefits of surveillance. Conclusion There is heterogeneity in postoperative follow-up for CRLM in the UK. High-quality prospective studies and randomised trials are necessary to elucidate the value of postoperative surveillance and identify optimal follow-up strategies.

Aims Suicidal ideation constitutes a central element of most theories of suicide and is the defining facet separating suicide from other causes of death such as accidents. However, despite a high worldwide prevalence, most research has focused on suicidal behaviours, such as completed suicide and suicide attempts, while the greater proportion who experienced ideation, which frequently precedes suicidal behaviour, have received much less attention. This study aims to examine the characteristics of those presenting to EDs with suicidal ideation and quantify the associated risk of suicide and other causes of death. Methods Retrospective cohort study was performed based on population-wide health administration data linked to data from the Northern Ireland Registry of Self-Harm and centrally held mortality records from April 2012 to December 2019. Mortality data, coded as suicide, all-external causes and all-cause mortality were analysed using Cox proportional hazards. Additional cause-specific analyses included accidental deaths, deaths from natural causes and drug and alcohol-related causes. Results There were 1,662,118 individuals aged over 10 years, of whom 15,267 presented to the ED with ideation during the study period. Individuals with ideation had a 10-fold increased risk of death from suicide (hazard ratio [HRadj] = 10.84, 95% confidence interval [CI] 9.18, 12.80) and from all-external causes (HRadj = 10.65, 95% CI 9.66, 11.74) and a threefold risk of death from all-causes (HRadj = 3.01, 95% CI 2.84, 3.20). Further cause-specific analyses indicated that risk of accidental death (HRadj = 8.24, 95% CI 6.29, 10.81), drug-related (HRadj = 15.17, 95% CI 11.36, 20.26) and alcohol-related (HRadj = 10.57, 95% CI 9.07, 12.31) has also significantly increased. There were few socio-demographic and economic characteristics that would identify which of these patients are most at risk of suicide or other causes of death. Conclusions Identifying people with suicidal ideation is recognized to be both important but difficult in practice; this study shows that presentations to EDs with self-harm or suicide ideation represent an important potential intervention point for this hard-to-reach vulnerable population. However, and unlike individuals presenting with self-harm, clinical guidelines for the management and recommended best practice and care of these individuals are lacking. Whilst suicide prevention may be the primary focus of interventions aimed at those experiencing self-harm and suicide ideation, death from other preventable causes, especially substance misuse, should also be a cause of concern.

Aims Suicide is a major public health concern. Identifying those most at risk is vital to ensure the implementation of effective interventions. Mental health (MH) is known to have a genetic component and parental MH is associated with offspring MH. However, little is known about the effect of parental psychopathology on offspring suicide risk. The aim of this study is to determine if children living with parents with poor MH are at an increased risk of poor MH, or death by suicide. Methods This population-wide cohort study linked data from the 2011 Northern Ireland Census to 6 years' death records (2011–2016). Information on MH status, in addition to other individual and household-level attributes, was derived from the 2011 Census. Logistic regression was utilised to examine the association between parental poor MH and offspring MH and suicide risk, with adjustment for socio-demographic characteristics. Results Overall, 11.6% of the cohort of 618 970 individuals were residing with parents who reported poor MH; 1.6% reported poor MH themselves, and 0.04% (n = 260) died by suicide. Living with a parent with poor MH increased the odds of offspring poor MH (OR = 2.80, 95% CI 2.59–3.03). After adjustment for age, gender, physical illness, socio-economic status and own MH, children living with 1 parent with poor MH were 76% more likely to die by suicide compared to children of parents who did not report poor MH (OR = 1.76, 95% CI 1.31–2.36). The effect size increased for children living with 2 parents with poor MH, and was higher in children aged under 24 years. Conclusions Living with a parent with poor MH is a significant risk factor for offspring poor MH and suicide, even after adjustment for personal MH status. When treating mental ill-health in parents, potential interventions for their children should also be considered.

Aim To assess consent forms in the new urgent laparoscopic cholecystectomy theatre (ESAC) list in the University Hospital of Wales. With procedure-specific consent forms becoming more regularly utilised, we assess the need for them in our Trust. Method We prospectively assessed the consent forms of the first 20 patients who were enrolled in ESAC. We measured the complications list against national standards to assess completeness, including any use of abbreviations and the overall legibility. To complete our assessment and for posterity, we called each patient and gave them an official questionnaire to ensure their understanding before, during and after surgery. Results We found that of the complications included in the ESAC consent forms, there was a high degree of variability. For example, 75% contained ‘bile leak’ and 55% ‘post-cholecystectomy syndrome’; both named examples in national guidelines. Additionally, while the vast majority were legible, 50% of the consent forms utilised abbreviations in their written sections. Lastly, patient understanding surrounding the details of the operation was sound, with the majority correctly identifying their surgery, what it entailed and what they were expected to do post-operatively. However, just over half were able to provide a moderately detailed list of the associated complications that may have occurred. Conclusions That the trust would benefit from a procedure-specific consent form (PSCF) to provide exhaustive information on procedure details, complications, and their rates, as well as mortality rates. Additionally, this would eliminate issues of legibility and usage of abbreviations. We anticipate that it will also improve patient understanding.

Background: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. Methods: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia–Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. Results: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. Conclusion: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.

Over the last 20 years, there have been significant changes in UK surgical training. Civilian surgical training may no longer prepare military surgeons for the range of skills they require on operations. One method to address gaps in knowledge or experience is to use telemedicine to facilitate specialist consultations from UK-based specialists to deployed medical teams. In the UK Defence Medical Services (DMS), this capability is called real-time clinical support (RTCS). RTCS provides a direct audio-visual link from a deployed location anywhere in the world to a supporting medical specialist in the UK. RTCS is currently delivered via a combination of off-the-shelf hardware and commercially available software. This article will outline the current use of RTCS, with emphasis on deployed surgical teams in austere environments, and discuss the advantages and limitations of this capability. However, it must be emphasised that no technology can be a substitute for clinical training and experience. Although several limitations remain, the authors believe that RTCS offers potential benefits for the DMS and could be an important tool aiding deployed clinicians. It can also be argued that by engaging with the concept now, the DMS can shape future developments in this sphere.

ObjectivesAt the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent, and interrupt, outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI).Study DesignWe undertook an ecological study using routinely available national data.MethodsWe used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes and, as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure.ResultsCare home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1,625 COVID-19 outbreaks (95% prediction interval 1,553 – 1,694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity.ConclusionsThese findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate effectiveness of the vaccines and the duration of their effects.

2017-2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, and with the funding organisations AEI, NWO, ECCyT and NSF Funding information, Allen-Perkins A, Magrach A, Dainese M, Garibaldi LA, Kleijn D, Rader R, Reilly JR, Winfree R, Lundin O, McGrady CM, Brittain C, Biddinger DJ, Artz DR, Elle E, Hoffman G, Ellis JD, Daniels J, Gibbs J, Campbell JW, Brokaw J, Wilson JK, Mason K, Ward KL, Gundersen KB, Bobiwash K, Gut L, Rowe LM, Boyle NK, Williams NM, Joshi NK, Rothwell N, Gillespie RL, Isaacs R, Fleischer SJ, Peterson SS, Rao S, Pitts-Singer TL, Fijen T, Boreux V, Rundlöf M, Viana BF, Klein AM, Smith HG, Bommarco R, Carvalheiro LG, Ricketts TH, Ghazoul J, Krishnan S, Benjamin FE, Loureiro J, Castro S, Raine NE, de Groot GA, Horgan FG, Hipólito J, Smagghe G, Meeus I, Eeraerts M, Potts SG, Kremen C, García D, Miñarro M, Crowder DW, Pisanty G, Mandelik Y, Vereecken NJ, Leclercq N, Weekers T, Lindstrom SAM, Stanley DA, Zaragoza-Trello C, Nicholson CC, Scheper J, Rad C, Marks EAN, Mota L, Danforth B, Park M, Bezerra ADM, Freitas BM, Mallinger RE, Oliveira da Silva F, Willcox B, Ramos DL, D da Silva E Silva F, Lázaro A, Alomar D, González-Estévez MA, Taki H, Cariveau DP, Garratt MPD, Nabaes Jodar DN, Stewart RIA, Ariza D, Pisman M, Lichtenberg EM, Schüepp C, Herzog F, Entling MH, Dupont YL, Michener CD, Daily GC, Ehrlich PR, Burns KLW, Vilà M, Robson A, Howlett B, Blechschmidt L, Jauker F, Schwarzbach F, Nesper M, Diekötter T, Wolters V, Castro H, Gaspar H, Nault BA, Badenhausser I, Petersen JD, Tscharntke T, Bretagnolle V, Willis Chan DS, Chacoff N, Andersson GKS, Jha S, Colville JF, Veldtman R, Coutinho J, Bianchi FJJA, Sutter L, Albrecht M, Jeanneret P, Zou Y, Averill AL, Saez A, Sciligo AR, Vergara CH, Bloom EH, Oeller E, Badano EI, Loeb GM, Grab H, Ekroos J, Gagic V, Cunningham SA, Åström J, Cavigliasso P, Trillo A, Classen A, Mauchline AL, Montero-Castaño A, Wilby A, Woodcock BA, Sidhu CS, Steffan-Dewenter I, Vogiatzakis IN, Herrera JM, Otieno M, Gikungu MW, Cusser SJ, Nauss T, Nilsson L, Knapp J, Ortega-Marcos JJ, González JA, Osborne JL, Blanche R, Shaw RF, Hevia V, Stout J, Arthur AD, Blochtein B, Szentgyorgyi H, Li J, Mayfield MM, Woyciechowski M, Nunes-Silva P, Halinski de Oliveira R, Henry S, Simmons BI, Dalsgaard B, Hansen K, Sritongchuay T, O'Reilly AD, Chamorro García FJ, Nates Parra G, Magalhães Pigozo C, Bartomeus I

Purpose: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non–small cell lung cancer (NSCLC). Patients and Methods: Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed. Results: Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change −28% [95% confidence interval (CI), −58.2 to −4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, −6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%–74%) lower in cohort 1 compared with cohort 2 (P = 0.004), adjusting for cohort, tumor volume, and baseline HV. A key pharmacodynamics endpoint was reduction in hypoxia-regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported. Conclusions: This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), (COVID-19) presents a challenge to UK society and its health system unprecedented in peace time.[1 2][1] Naturally, many have reached for wartime metaphors to capture the pandemic’s impact and the demand for resilience, community and

Background Research from the United States (US) provides compelling evidence of disparities in breast screening uptake for women with mental illness, yet few attempts have been made to examine this association in the United Kingdom (U.K) where healthcare is free at the point of use. It is well established that mental illness is not evenly distributed across the population. For example, mental illness is more prevalent in individuals who are unmarried, socially deprived, and residing in urban areas. Interestingly, these attributes are also strong predictors of lower attendance at breast screening, and it is possible that this may be explained by the increased prevalence of mental illness in these individuals. This study aims to examine the impact of self-reported poor mental health on attendance at breast screening in the United Kingdom (UK), and to what extent this explains socio-demographic inequalities in uptake. Methods Breast screening records were linked to 2011 Census data within the Northern Ireland Longitudinal Study (NILS). This identified a cohort of 57,328 women who were followed through one complete three-year screening cycle of the National Health Service (NHS) breast screening programme. Poor mental health was identified using responses to question 23 of the Northern Ireland 2011 Census which asked, ‘Do you have any of the following conditions, which have lasted, or are expected to last, at least 12 months?’ to which ‘An emotional, psychological or mental health condition (such as depression or schizophrenia)’ was a possible response. Information on individual and household-level attributes was also derived from Census records. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals of attendance at breast screening. Results 10.7% of women in the cohort reported poor mental health, and in fully-adjusted analyses, these individuals were 23% less likely to attend breast screening (OR 0.77: 0.73–0.82). Although poor mental health was a strong predictor of screening uptake, it only explained a minimal degree of the observed inequalities in uptake by socio-economic status and marital status, and did not explain any of the variation by area of residence. Furthermore, there was no evidence of effect modification between poor mental health and any other socio-demographic determinant of screening uptake. Conclusion This study provides novel evidence of inequalities in breast screening uptake for women with self-reported poor mental health in the UK. Targeted interventions are required to improve screening uptake in individuals with mental illness to optimise the mortality benefits achieved through population-wide screening.

International audience; This study provides predictive equations for Shannon's information in a finite population, which are intuitive and simple enough to see wide scale use in molecular ecology and population genetics. A comprehensive profile of genetic diversity contains three complementary components: numbers of allelic types, Shannon's information and heterozygosity. Currently heterozygosity has greater resources than Shannon's information, such as more predictive models and integration into more mainstream genetics software. However, Shannon's information has several advantages over heterozygosity as a measure of genetic diversity, so it is important to develop Shannon's information as a new tool for molecular ecology. Past efforts at making forecasts for Shannon's information in specific molecular ecology scenarios mostly dealt with expectations for Shannon's information at genetic equilibrium, but dynamic forecasts are also vital. In particular, we must be able to predict loss of genetic diversity when dealing with finite populations, because they risk losing genetic variability, which can have an adverse effect on their survival. We present equations for predicting loss of genetic diversity measured by Shannon's information. We also provide statistical justification for these models by assessing their fit to data derived from simulations and managed, replicated laboratory populations. The predictive models will enhance the usefulness of Shannon's information as a measure of genetic diversity; they will also be useful in pest control and conservation.

BACKGROUND Little research exists in the teaching of evidence-based dentistry (EBD) to students in the fields of dental hygiene, dental nursing and orthodontic therapy. This study aims to analyse the effect of a 1-day EBD programme on knowledge and confidence whilst also gaining insight into students' experience of the intervention. METHOD A mixed methods study was utilised with explanatory sequential design. The population consisted of dental hygiene (DH), dental nursing (DN) and orthodontic therapy (OT) students (N = 44). The intervention consisted of a 1-day active learning EBD programme, delivered via group projects and lectures. In the initial quantitative phase, a standardised questionnaire pre- and post -intervention measured changes in confidence for all participants, whilst change in knowledge was measured for DH and OT students only. Following this, focus groups were scheduled for all members of each discipline 3 months post-intervention for DN and 2 months post-intervention for DH and OT students. Semi-structured focus group schedules were drawn up, and groups organised according to the outcomes of quantitative data analysis. Qualitative results were analysed using a deductive adaptation of Burnard's thematic content analysis. RESULTS Forty-two students took part (94.45%) in this study. Median knowledge scores increased from zero to two of five (P

Background The rheumatoid arthritis (RA) Treat to Target (T2T) recommendations1 defined in 2010 aimed to support clinicians to achieve optimal therapeutic outcomes for their patients. Objectives 38 hospitals prospectively audited management of newly diagnosed RA patients to determine compliance with the T2T recommendations and therapeutic outcomes achieved. Methods From April 2012 to September 2016 and upon diagnosis of RA, data on disease history, management and clinical outcomes were collected prospectively in a web based tool. Follow up to date provides data for up to 24 months from diagnosis (baseline). Results 1571 patients were recruited in 38 centres, with 12 months9 follow up for 713 patients and of these 269 also had 24 months9 follow up. 1021 (65%) patients were female and 1360 (87%) had a treatment target documented at baseline (1235 [79%] disease activity score 28 (DAS28) remission and 125 [8%] low disease activity state (LDAS)). DAS28 remission is defined as DAS28 Conclusions The results suggest that more patients with a target set at baseline are in remission at 12 months and at 24 months than those without a target set. Number of visits, number of DAS28 scores and starting dual therapy within 6 months do not appear to affect the proportion of patients in remission at 12 months, but active management in the first 12 months (>4 visits, >4 DAS28 scores) does appear to be associated with more patients in remission at 24 months. Thus we conclude that treating RA early and aggressively, in line with the T2T guidelines, leads to sustained clinical improvement. References Smolen et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631–637. Disclosure of Interest A. L. Tan Consultant for: I have received honoraria from AbbVie Ltd., M. Buch Consultant for: has received previous honorarium/consultancy with Abbvie, Astra Zeneca, Bristol-Myers Squibb, Lilly, Roche-Chugai, Sandoz and research grants from Roche and Pfizer., D. O9Reilly Consultant for: has been paid research/consultancy fees/other honoraria by Amgen, Abbvie, MSD, pH Associates, Roche, UCB and Wyeth., T. Sheeran Consultant for: has been paid consultancy fees by Roche, AbbVie, Novatis and Pfizer., A. Bishop-Bailey Employee of: I am an employee of pH Associates, the company commissioned by Abbvie to design and implement the study, as well as perform analysis and presentation/publication of the study data., G. Nock Employee of: I am an employee of pH Associates, the company commissioned by Abbvie to design and implement the study, as well as perform analysis and presentation/publication of the study data., S. Chitale Consultant for: has been on an advisory board for Abbvie and Pfizer, and has received educational grants from Abbvie, Pfizer and UCB., P. Emery Consultant for: undertaken clinical trials and provided expert advice to Pfizer,MSD,Abbvie,BMS,UCB,Roche,Novartis,Samsung, Sandoz and Lilly

The Decision Analytic Model for Oral Pre-cancerous Lesions. Patients who have already undergone biopsy are diagnosed either by histopathology, where the dysplasia is graded as severe, moderate or mild based on the extent of the architectural and cytological changes, or with histopathology and Stratictye™, where patients in each dysplasia grading are further classified as high, medium, or low risk of developing oral cancer based on the result of the Stratictye™ test. These categorizations are mapped in mutually exclusive pathways. Table S1. Qualitative and Quantitative Approaches to Conduct Early CEA. Table S2. Defining the Scope of Early Cost-effectiveness (CEA) Model. Table S3. Four Key Model Assumptions. Table S4. The Literature Search Strategy. Figure S2. The PRISMA flow chart. Table S5. The characteristics of the included studies [30–34]. Figure S3. The forest plot by RevMan [35]. Table S6. Questionnaire for Oral and Maxillofacial Surgeons. Table S7. The outcome of the Questionnaires. Table S8. Costing Details [36]. Table S9. Definitions of the model input parameters. Figure S4. The scattered plot of 5000 Monte Carlo simulations. (DOCX 2425 kb)

The Haywood Medical Society met in June 2011 to discuss issues surrounding the preparedness of both civilian and military emergency services to deal with a CBRN threat.

We consistently incorporate Yang Mills matter fields into string corrected (deformed), D=10, N=1 Supergravity. We solve the Bianchi identities within the framework of the modified beta function favored constraints to second order in the string slope parameter $\g$ also including the Yang Mills fields. In the torsion, curvature and H sectors we find that a consistent solution is readily obtained with a Yang Mills modified supercurrent $A_{abc}$. We find a solution in the F sector following our previously developed method., Comment: 11 pages, LaTeX file, PACS number: 04.65.+e

The article critically discusses parenteral delivery of self-assembled lipid or amphiphile nanoparticles, in the form of aggregated clusters or particles (capsules). The end-product or drug form is for application by administration of the medicine active in encapsulated form. This is used for site-specific cell manipulation and clinical therapy and introduces this directly to the body via the systemic route. The technology discussed represents a platform formulation that can be modified for a range of specific cellular targets. The components of the nanoparticle are assembled piece-by-piece and this provides an element of design flexibility, with the core particle being built-up in a succession of layers to ensure circulatory longevity and storage stability. This strategy excludes a more generalised delivery and widespread lack of active targeting and thus low dosage rather than avoidance of target, which is at best detrimental and at worst catastrophic in terms of non-targeted cell death. However, in some cases such as the AmBisome nanoparticle this drug delivery approach can work. This "better focussing" is achieved by a dual use of i) biocompatible particle coating chemistry and a ii) cell-ligand imprinted nanoparticle surface that furnishes the engineered nanoparticle with a recognition element to form a complex but more efficacious dispersible fusogenic pro-drug moiety. Non-targeted delivery of drugs such as those commonly forming the basis of transdermal delivery have been generically based on topical or adhesive patch-based delivery (emulsions) systems. This procedure even with recent advancements and patents is customarily inefficient in dosage and payload delivery, inconsistent in terms of product potency and inflexible to further modification or purpose-related enhancement. The assembly and delivery methodologies discussed here take the new experimental medicine and review them in a more focused and purposeful therapy-constructed manner. It is the use of a smart platform technology that is responsible for increased efficacy when applied to the disorder of interest.