Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Effect of a Web-Based Behavior Change Program on Weight Loss and Cardiovascular Risk Factors in Overweight and Obese Adults at High Risk of Developing Cardiovascular Disease:Randomized Controlled Trial

BACKGROUND: Web-based programs are a potential medium for supporting weight loss because of their accessibility and wide reach. Research is warranted to determine the shorter- and longer-term effects of these programs in relation to weight loss and other health outcomes.

OBJECTIVE: The aim was to evaluate the effects of a Web-based component of a weight loss service (Imperative Health) in an overweight/obese population at risk of cardiovascular disease (CVD) using a randomized controlled design and a true control group.

METHODS: A total of 65 overweight/obese adults at high risk of CVD were randomly allocated to 1 of 2 groups. Group 1 (n=32) was provided with the Web-based program, which supported positive dietary and physical activity changes and assisted in managing weight. Group 2 continued with their usual self-care (n=33). Assessments were conducted face-to-face. The primary outcome was between-group change in weight at 3 months. Secondary outcomes included between-group change in anthropometric measurements, blood pressure, lipid measurements, physical activity, and energy intake at 3, 6, and 12 months. Interviews were conducted to explore participants' views of the Web-based program.

RESULTS: Retention rates for the intervention and control groups at 3 months were 78% (25/32) vs 97% (32/33), at 6 months were 66% (21/32) vs 94% (31/33), and at 12 months were 53% (17/32) vs 88% (29/33). Intention-to-treat analysis, using baseline observation carried forward imputation method, revealed that the intervention group lost more weight relative to the control group at 3 months (mean -3.41, 95% CI -4.70 to -2.13 kg vs mean -0.52, 95% CI -1.55 to 0.52 kg, P<.001), at 6 months (mean -3.47, 95% CI -4.95 to -1.98 kg vs mean -0.81, 95% CI -2.23 to 0.61 kg, P=.02), but not at 12 months (mean -2.38, 95% CI -3.48 to -0.97 kg vs mean -1.80, 95% CI -3.15 to -0.44 kg, P=.77). More intervention group participants lost ≥5% of their baseline body weight at 3 months (34%, 11/32 vs 3%, 1/33, P<.001) and 6 months (41%, 13/32 vs 18%, 6/33, P=.047), but not at 12 months (22%, 7/32 vs 21%, 7/33, P=.95) versus control group. The intervention group showed improvements in total cholesterol, triglycerides, and adopted more positive dietary and physical activity behaviors for up to 3 months verus control; however, these improvements were not sustained.

CONCLUSIONS: Although the intervention group had high attrition levels, this study provides evidence that this Web-based program can be used to initiate clinically relevant weight loss and lower CVD risk up to 3-6 months based on the proportion of intervention group participants losing ≥5% of their body weight versus control group. It also highlights a need for augmenting Web-based programs with further interventions, such as in-person support to enhance engagement and maintain these changes.

Performance of a Novel Molecular Method in the Diagnosis of Late-Onset Sepsis in Very Low Birth Weight Infants

OBJECTIVE: To compare the use of a generic molecular assay to 'standard' investigations used to assist the diagnosis of late onset bacterial sepsis in very low birth weight infants (VLBW, <1500g).

METHODS: VLBW infants, greater than 48 hours of age, who were clinically suspected to have sepsis were investigated using standard tests (full blood count, C-reactive protein (at presentation) and blood culture), in addition, blood was taken for a universal molecular assay (16S rRNA reverse transcriptase PCR) for comparison. Clinical data were recorded during the suspected infection episode. A validated sepsis score (NEO-KISS) was used to retrospectively determine the presence of sepsis (independent of blood culture). The performance of each of the tests were compared by sensitivity, specificity, positive/negative likihood ratios (+/-LR) and postive/negative predictive values (PPV/NPV).

RESULTS: Sixty-five babies with suspected clinical sepsis were prospectively included. The performance indicators are presented with 95% confidence limits. For the detection of bacteria, blood culture had sensitivity of 0.57 (0.34-0.78), specificity of 0.45 (0.30-0.61); +LR of 1.05 (0.66-1.66) and-LR of 0.94 (0.52-1.7); PPV of 33.3 (18.56-50.97) and NPV of 68.97 (49.17-87.72). Serum CRP had sensitivity of 0.92 (0.64-1) and specificity of 0.36 (0.17-0.59); +LR of 1.45 (1-2.1) and-LR of 0.21 (0.03-1.5); PPV of 44.46 (26.6-66.6) and NPV of 88.9 (51.8-99.7). The universal molecular assay had sensitivity of 0.76 (0.53-0.92), specificity of 0.95 (0.85-0.99); +LR of 16.8 (4.2-66.3) and-LR of 0.25 (0.1-0.5); PPV of 88.9 (65.3-98.6) and NPV of 89.4 (76.9-96.5).

CONCLUSIONS: In VLBW infants this universal molecular assay performed better in the diagnosis of late onset sepsis (LOS) than blood culture and CRP. Further development is required to explore and improve the performance of the assay in real-time diagnosis.

Wing Panel Design with Novel Skin-Buckling Containment Features

The impact of buckling containment features on the stability of thin-gauge fuselage, metallic stiffened panels has previously been demonstrated. With the continuing developments in manufacturing technology, such as welding, extrusion, machining, and additive layer manufacture, understanding the benefits of additional panel design features on heavier applications, such as wing panels, is timely. This compression testing of thick-gauge panels with and without buckling containment features has been undertaken to verify buckling and collapse behaviors and validate sizing methods. The experimental results demonstrated individual panel mass savings on the order of 9%, and wing cover design studies demonstrated mass savings on the order of 4 to 13%, dependent on aircraft size and material choice.

Still Unequal at Birth: Birth Weight, Socioeconomic Status and Outcomes at Age 9

The prevalence of low birth weight is an important aspect of public health which has been linked to increased risk of infant death, increased cost of care, and a range of later life outcomes. Using data from a new Irish cohort study, I document the relationship between birth weight and socio-economic status. The association of maternal education with birth weight does not appear to be due to the timing of birth or complications during pregnancy, even controlling for a wide range of background characteristics. However, results do suggest intergenerational persistence in the transmission of poor early life conditions. Birth weight predicts a number of outcomes at age 9, including test scores, hospital stays and health. An advantage of the data is that I am able to control for a number of typically unmeasured variables. I determine whether parental investments (as measured by the quality of interaction with the child, parenting style, or school quality) mediate the association between birth weight and later indicators. For test scores, there is evidence of non-linearity, and boys are more adversely affected than girls. I also consider whether there are heterogeneous effects by ability using quantile regression. These results are consistent with a literature which finds that there is a causal relationship between early life conditions and later outcomes.

Kids just wanna have fun: Children's experiences of a weight management programme

Objectives: To explore children's accounts of their experiences of the UK‘s largest childhood obesity programme, MEND (Mind, Exercise, Nutrition…Do it!) (See www.mendprogramme.org). Design: Semi-structured interviews were conducted with children who had completed the MEND obesity programme. Interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis (IPA). Method Fourteen children spanning diverse areas of London comprised this study (eight male, six female), aged between 11 and 14 years and in secondary school. Participants were interviewed a year after completing one of the London-based MEND obesity programmes. Results: This article focuses on the most common and striking theme to emerge from the original dataset (The complete analysis may be found in L. Watson, Unpublished doctoral thesis): Fun. Subthemes were: ‘going with the flow’; active participation in activities that led to new experiences (‘actually doing it’ – seeing the fun side); the importance of others in the experience of fun (‘you do games in unity’ – ‘it's not as fun on your own’). Conclusion: Children have fun when engaged in interactive and varied activities with opportunity for individual feedback and improvement. When designing childhood obesity programmes, conditions that optimise children's experience of fun should be emphasised over didactic and risk-heavy information pertaining to childhood obesity.

Role of the different actin genes during extrusion of capping protein mutant cells in the Drosophila wing blade epithelium

Dissertação mest., Biotecnologia, Universidade do Algarve, 2008

Estimating depth and explosive charge weight for an extremely shallow underwater explosion of the ROKS Cheonan sinking in the Yellow Sea

We estimated the detonation depth and net explosive weight for a very shallow underwater explosion using cutoff frequencies and spectral analysis. With detonation depth and a bubble pulse the net explosive weight for a shallow underwater explosion could simply be determined. The ray trace modeling confirms the detonation depth as a source of the hydroacoustic wave propagation in a shallow channel. We found cutoff frequencies of the reflection off the ocean bottom to be 8.5 Hz, 25 Hz, and 43 Hz while the cutoff frequency of the reflection off the free surface to be 45 Hz including 1.01 Hz for the bubble pulse, and also found the cutoff frequency of surface reflection to well fit the ray-trace modeling. We also attempted to corroborate our findings using a 3D bubble shape modeling and boundary element method. Our findings led us to the net explosive weight of the underwater explosion offshore of Baengnyeong-do for the ROKS Cheonan sinking to be approximately 136 kg TNT at a depth of about 8 m within an ocean depth of around 44 m. © 2015 Elsevier B.V.

AB1258­HPR pilot study: does a mediterranean diet­based weight loss programme improve health outcomes in overweight older women with knee osteoarthritis?

Osteoarthritis (OA) is one of the leading causes of pain and disability among older adults, particularly women. Pain and mobility disability are major consequences of knee OA which and can interfere with the functional autonomy of elderly and thus, making it difficult to perform activities of daily living. Evidence suggests that obesity is strongly linked to knee OA and that non­pharmacological therapy should be based on physical activity and weight loss in case of overweight and obesity. A positive relationship between adherence to the Mediterranean diet and health outcomes has been widely discussed in scientific literature, including its potential benefits in weight loss.

The attractive female body weight and female body dissatisfaction in 26 countries across 10 world regions: results of the International Body Project I

This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.

Association between birth weight and neuromotor performance: a twin study

The development of neonatal intensive care has led to an increase in the prevalence of children with low birth weight and associated morbidity. The objectives of this study are to verify (1) The association between birth weight (BW) and neuromotor performance? (2) Is the neuromotor performance of twins within the normal range? (3) Are intra-pair similarities in neuromotor development of Monozygotic (MZ) and Disygotic (DZ) twins of unequal magnitude? The sample consisted of 191 children (78 MZ and 113 DZ), 8.9+3.1 years of age and with an average BW of 2246.3+485.4g. In addition to gestational characteristics, sports participation and Zurich Neuromotor Assessment (ZNA) were observed at childhood age. The statistical analysis was carried out with software SPSS 18.0, the STATA 10 and the ZNA performance scores. The level of significance was 0.05. For the neuromotor items high intra and inter-investigator reliabilities were obtained (0.793

The Role of Actin-Capping Protein and Src signalling in tissue growth and apoptosis during Drosophila wing development

Dissertation presented to obtain the Ph.D degree in Developmental Biology