Architected cellular ceramics with tailored stiffness via direct foam writing.

Hierarchical cellular structures are ubiquitous in nature because of their low-density, high-specific properties, and multifunctionality. Inspired by these systems, we created lightweight ceramic architectures composed of closed-cell porous struts patterned in the form of hexagonal and triangular honeycombs by direct foam writing. The foam ink contains bubbles stabilized by attractive colloidal particles suspended in an aqueous solution. The printed and sintered ceramic foam honeycombs possess low relative density (∼6%). By tailoring their microstructure and geometry, we created honeycombs with different modes of deformation, exceptional specific stiffness, and stiffness values that span over an order of magnitude. This capability represents an important step toward the scalable fabrication of hierarchical porous materials for applications, including lightweight structures, thermal insulation, tissue scaffolds, catalyst supports, and electrodes.

Trends of serum phospholipid fatty acids over time in rural Uganda: evidence of nutritional transition?

Non-communicable diseases are projected to become the most common causes of death in Africa by 2030. The impact on health of epidemiological and nutritional transitions in sub-Saharan Africa remains unclear. To assess the trends of dietary fatty acids over time in Uganda, we examined fatty acids in serum collected from individuals in rural south-west Uganda, at three time points over two decades. Independent cross-sectional samples of 915 adults and children were selected from the general population cohort in 1990 (n 281), 2000 (n 283) and 2008 (n 351). Serum phospholipid fatty acids were measured by GC. Multivariate regression analyses were performed to compare the geometric means of fatty acids by time period. Serum fatty acid profiling showed high proportions of SFA, cis-MUFA and industrial trans-fatty acids (iTFA), likely to be biomarkers of high consumption of palm oil and hydrogenated fats. In contrast, proportions of n-6 and n-3 PUFA from vegetable oils and fish were low. From 1990 to 2008, serum phospholipids showed increases in absolute amounts of SFA (17·3 % increase in adults and 26·4 % in children), MUFA (16·7 % increase in adults and 16·8 % in children) and n-6:n-3 PUFA (40·1 % increase in adults and 39·8 % in children). The amount of elaidic acid, iTFA from hydrogenated fats, increased in children (60·1 % increase). In this rural Ugandan population, we show evidence of unfavourable trends over time of dietary fatty acids.

Menstrual health and school absenteeism among adolescent girls in Uganda (MENISCUS): a feasibility study.

BACKGROUND: Management of menstruation can present substantial challenges to girls in low-income settings. In preparation for a menstrual hygiene intervention to reduce school absenteeism in Uganda, this study aimed to investigate menstruation management practices, barriers and facilitators, and the influence of menstruation on school absenteeism among secondary school students in a peri-urban district of Uganda. METHODS: Qualitative and quantitative studies were conducted among consenting girls and boys aged 14-17 years in four secondary schools in Entebbe sub-District, Uganda. Methods included group and in-depth interviews with students, a quantitative cross-sectional questionnaire, a prospectively self-completed menstrual diary, key informant interviews with policy makers, and observations of school water, sanitation and hygiene facilities. Multiple logistic regression was used to assess factors associated with school absenteeism during the most recent menstrual period. RESULTS: Girls reported substantial embarrassment and fear of teasing related to menstruation in the qualitative interviews, and said that this, together with menstrual pain and lack of effective materials for menstrual hygiene management, led to school absenteeism. All policy makers interviewed reported poverty and menstruation as the key factors associated with school attendance. The 352 girls with questionnaire data had a median age of 16 (inter-quartile range (IQR) = 15,16) years, with median age at menarche of 13 (IQR = 13,14) years. Of these, 64 girls (18.7%) reported having stained their clothes and 69 (19.7%) reported missing at least 1 day of school, during their most recent period. Missing school during the most recent period was associated with physical symptoms (headache (odds ratio (OR) = 2.15, 95%CI:1.20, 3.86), stomach pain (OR = 1.89, 95%CI:0.89, 4.04), back pain (OR = 1.75, 95%CI:0.97, 3.14), and with changing protection 4 or more times per 24 h period (OR = 2.08, 95%CI:1.06, 4.10). In the diary sub-study among 40 girls, school absence was reported on 28% of period-days, compared with 7% of non-period days (adjusted odds ratio = 5.99, 95%CI:4.4, 8.2; p < 0.001). CONCLUSION: In this peri-urban Ugandan population, menstruation was strongly associated with school attendance. Evaluation of a menstrual management intervention that address both psychosocial (e.g. self-confidence, attitudes) and physical (e.g. management of pain, use of adequate menstrual hygiene materials, improved water and sanitation facilities) aspects of menstruation are needed.

Changes in conceptions in women younger than 18 years and the circumstances of young mothers in England in 2000-12: an observational study.

BACKGROUND: In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals. METHODS: In this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994-98 to 2009-13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990-91), Natsal-2 (1999-2001), and Natsal-3 (2010-12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18-24 years; and the prevalence of participation in education, work, and training in young mothers. FINDINGS: Conception rates in women younger than 18 years declined steadily from their peak in 1996-98 and more rapidly from 2007 onwards. More deprived areas and those receiving greater Teenage Pregnancy Strategy-related investment had higher rates of conception in 1994-98 and had greater declines to 2009-13. Regression analyses assessing the association between Teenage Pregnancy Strategy funding and decline in conception rates in women younger than 18 years showed an estimated reduction in the conception rate of 11.4 conceptions (95% CI 9.6-13.2; p<0.0001) per 1000 women aged 15-17 years for every £100 Teenage Pregnancy Strategy spend per head and a reduction of 8.2 conceptions (5.8-10.5; p<0.0001) after adjustment for socioeconomic deprivation and region. The association between conception in women younger than 18 years and lower socioeconomic status weakened slightly between Natsal-2 and Natsal-3. The prevalence of participation in education, work, or training among young women with a child conceived before age 18 years was low, but the odds of them doing so doubled between Natsal-2 and Natsal-3 (odds ratio 1.99, 95% CI 0.99-4.00). INTERPRETATION: A sustained, multifaceted policy intervention involving health and education agencies, alongside other social and educational changes, has probably contributed to a substantial and accelerating decline in conceptions in women younger than 18 years in England since the late 1990s. FUNDING: Medical Research Council, Wellcome Trust, Economic and Social Research Council, and Department of Health.

The prevalence of unplanned pregnancy and associated factors in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales). METHOD: We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of 15,162 men and women aged 16-74 years in Britain, including 5686 women of child-bearing age (16-44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course. FINDINGS: 9·7% of women aged 16-44 years had pregnancies with known outcome in the year before interview, of which 16·2% (95% CI 13·1-19·9) scored as unplanned, 29·0% (25·2-33·2) as ambivalent, and 54·8% (50·3-59·2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1·5% (1·2-1·9). Pregnancies in women aged 16-19 years were most commonly unplanned (45·2% [30·8-60·5]). However, most unplanned pregnancies were in women aged 20-34 years (62·4% [50·2-73·2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2·85 [95% CI 1·77-4·57], current smoking (2·47 [1·46-4·18]), recent use of drugs other than cannabis (3·41 [1·64-7·11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1·90 [1·14-3·08]), reporting higher frequency of sex (2·11 [1·25-3·57] for five or more times in the past 4 weeks), receiving sex education mainly from a non-school-based source (1·84 [1·12-3·00]), and current depression (1·96 [1·10-3·47]). INTERPRETATION: The increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy. Our data offer scope for primary prevention aimed at reducing the rate of unplanned conceptions, and secondary prevention aimed at modification of health behaviours and health disorders in unplanned pregnancy that might be harmful for mother and child. FUNDING: Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.

Lifetime prevalence, associated factors, and circumstances of non-volitional sex in women and men in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: Sexual violence is increasingly recognised as a public health issue. Information about prevalence, associated factors, and consequences for health in the population of Britain (England, Scotland, and Wales) is scarce. The third National Survey of Sexual Health Attitudes and Lifestyles (Natsal-3) is the first of the Natsal surveys to include questions about sexual violence and the first population-based survey in Britain to explore the issue outside the context of crime. METHODS: Between Sept 6, 2010, and Aug 31, 2012, we did a probability sample survey of women and men aged 16-74 years living in Britain. We asked participants about their experience of sex against their will since age 13 years and the circumstances surrounding the most recent occurrence. We explored associations between ever experiencing non-volitional sex and a range of sociodemographic, health, and behavioural factors. We used logistic regression to estimate age-adjusted odds ratios to analyse factors associated with the occurrence of completed non-volitional sex in women and men. FINDINGS: We interviewed 15,162 people. Completed non-volitional sex was reported by 9·8% (95% CI 9·0-10·5) of women and 1·4% (1·1-1·7) of men. Median age (interdecile range) at most recent occurrence was 18 years (14-32) for women and 16 years (13-30) for men. Completed non-volitional sex varied by family structure and, in women, by age, education, and area-level deprivation. It was associated with poor health, longstanding illness or disability, and treatment for mental health conditions, smoking, and use of non-prescription drugs in the past year in both sexes, and with binge drinking in women. Completed non-volitional sex was also associated with reporting of first heterosexual intercourse before 16 years of age, same-sex experience, more lifetime sexual partners, ever being diagnosed with a sexually transmitted infection, and low sexual function in both sexes, and, in women, with abortion and pregnancy outcome before 18 years of age. In most cases, the person responsible was known to the individual, although the nature of the relationship differed by age at most recent occurrence. Participants who were younger at interview were more likely to have told someone about the event and to have reported it to the police than were older participants. INTERPRETATION: These data provide the first population prevalence estimates of non-volitional sex in Britain. We showed it to be mainly an experience of young age and strongly associated with a range of adverse health outcomes in both women and men. FUNDING: Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.

Prevalence of post-traumatic stress disorder and validity of the Impact of Events Scale - Revised in primary care in Zimbabwe, a non-war-affected African country.

BACKGROUND: A critical step in research on the epidemiology of post-traumatic stress disorder (PTSD) in low-resource settings is the validation of brief self-reported psychometric tools available in the public domain, such as the Impact Event Scale - Revised (IES-R). AIMS: We aimed to investigate the validity of the IES-R in a primary healthcare setting in Harare, Zimbabwe. METHOD: We analysed data from a survey of 264 consecutively sampled adults (mean age 38 years; 78% female). We estimated the area under the receiver operating characteristic curve and sensitivity, specificity and likelihood ratios for different cut-off points of the IES-R, against a diagnosis of PTSD made using the Structured Clinical Interview for DSM-IV. We performed factor analysis to evaluate construct validity of the IES-R. RESULTS: The prevalence of PTSD was 23.9% (95% CI 18.9-29.5). The area under the curve for the IES-R was 0.90. At a cut-off of ≥47, the sensitivity of the IES-R to detect PTSD was 84.1 (95% CI 72.7-92.1) and specificity was 81.1 (95% CI 75.0-86.3). Positive and negative likelihood ratios were 4.45 and 0.20, respectively. Factor analysis revealed a two-factor solution, with both factors showing good internal consistency (Cronbach's factor-1 α = 0.95, factor-2 α = 0.76). In a post hoc analysis, we found the brief six-item IES-6 also performed well, with an area under the curve of 0.87 and optimal cut-off of 15. CONCLUSIONS: The IES-R and IES-6 had good psychometric properties and performed well for indicating possible PTSD, but at higher cut-off points than those recommended in the Global North.

Hierarchically Porous Ceramics via Direct Writing of Binary Colloidal Gel Foams.

Hierarchically porous ceramics with a high specific surface area and interconnected porosity may find potential application as particulate filters, catalyst supports, and battery electrodes. We report the design and programmable assembly of cellular ceramic architectures with controlled pore size, volume, and interconnectivity across multiple length scales via direct foam writing. Specifically, binary colloidal gel foams are created that contain entrained bubbles stabilized by the irreversible adsorption of attractive alumina and carbon (porogen) particles at their air-water interfaces. Composition effects on foam ink rheology and printing behavior are investigated. Sintered ceramic foams exhibited specific permeabilities that increased from 2 × 10-13 to 1 × 10-12 m2 and compressive strengths that decreased from 40 to 1 MPa, respectively, with increasing specific interfacial area. Using direct foam writing, 3D ceramic lattices composed of open-cell foam struts were fabricated with tailored mechanical properties and interconnected porosity across multiple length scales.

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

Risk factors for breast cancer among Filipino women in Manila.

Age-adjusted incidence rates of breast cancer vary greatly worldwide with highest rates found in the typically 'westernised' countries of North America and Europe. Much lower rates are observed in Asian and African populations but an exception to this has been reported for the Manila Cancer Registry in the Philippines. The reason for this high rate is unknown but may be associated with the change in lifestyle that has occurred in urban Manila since the 1960s. In 1995, a randomised controlled trial was set up in Manila to evaluate the feasibility of a screening intervention by clinical breast examination as an alternative to mammography. The cohort of 151,168 women was followed-up to 2001 for cancer incidence and a nested case-control study carried out. This aimed to evaluate the increase in breast cancer risk associated with known risk factors. Increased risks were seen for a high level of education (OR = 1.9 95%CI 1.1-3.3 for education stopped at > or =13 versus <13 years), nulliparity (OR = 5.0 95% CI 2.5-10.0 for nulliparity versus five or more children), and late age at first birth (OR = 3.3 95% CI 1.3-8.3 for age > or =30 versus <20 years). We found no association with excess body weight, height, use of exogenous hormones or alcohol consumption. From this study, the recognised "classical" risk factors do not fully explain the high breast cancer incidence in Metro Manila, especially when compared to other urban Asian populations. We conclude that it is too simplistic to ascribe the high risk to 'westernisation'.

Developing sustainable capacity-building in mental health research: implementation outcomes of training of trainers in systematic reviewing.

Less than 1% of biomedical research papers originate in Africa. Locally relevant mental health research, including synthesis of existing evidence, is essential for developing interventions and strengthening health systems, but institutions may lack the capacity to deliver training on systematic reviewing for publication in international journals. This paper describes the development and implementation of a training-of-trainers (ToT) course on systematic reviewing. The ToT prepared junior faculty ('trainers') from universities in Ethiopia, Malawi, and Zimbabwe to lead a five-day systematic reviewing workshop. Using an evaluation framework based on implementation science outcomes, the feasibility of the ToT was assessed by tracking the number of workshops the trainers subsequently conducted and the number of trainers and trainees who participated; acceptability was assessed through post-workshop surveys on trainee perspectives; impact was evaluated through trainee scores on a 15-item multiple choice test on systematic reviewing concepts; and sustainability was assessed based on whether the workshop was integrated into university curricula. Twelve trainers (86% of those trained) facilitated a total of seven workshops in their home countries (total 103 trainees). The first workshop run in each country was evaluated, and there was a significant improvement in mean knowledge scores between pre- and post-tests among trainees (MD= 3.07, t= 5.90, 95% CI 2.02-4.11). In two of the three countries, there are efforts to integrate the systematic review workshop into university curricula. The cost of the workshop led by the international trainer was $1480 per participant, whereas the trainer-led workshops cost approximately $240 per participant. Overall, ToT is relatively new to research capacity building, although it has been used widely in clinical settings. Our findings suggest ToT is a promising, low-cost way to develop both technical skills of individuals and the pedagogical capacity of universities, and to promote sustainability of research capacity building programs that often have time-limited grant funding.

Patient Health Questionnaire-9 scores do not accurately estimate depression prevalence: individual participant data meta-analysis.

OBJECTIVES: Depression symptom questionnaires are not for diagnostic classification. Patient Health Questionnaire-9 (PHQ-9) scores ≥10 are nonetheless often used to estimate depression prevalence. We compared PHQ-9 ≥10 prevalence to Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) major depression prevalence and assessed whether an alternative PHQ-9 cutoff could more accurately estimate prevalence. STUDY DESIGN AND SETTING: Individual participant data meta-analysis of datasets comparing PHQ-9 scores to SCID major depression status. RESULTS: A total of 9,242 participants (1,389 SCID major depression cases) from 44 primary studies were included. Pooled PHQ-9 ≥10 prevalence was 24.6% (95% confidence interval [CI]: 20.8%, 28.9%); pooled SCID major depression prevalence was 12.1% (95% CI: 9.6%, 15.2%); and pooled difference was 11.9% (95% CI: 9.3%, 14.6%). The mean study-level PHQ-9 ≥10 to SCID-based prevalence ratio was 2.5 times. PHQ-9 ≥14 and the PHQ-9 diagnostic algorithm provided prevalence closest to SCID major depression prevalence, but study-level prevalence differed from SCID-based prevalence by an average absolute difference of 4.8% for PHQ-9 ≥14 (95% prediction interval: -13.6%, 14.5%) and 5.6% for the PHQ-9 diagnostic algorithm (95% prediction interval: -16.4%, 15.0%). CONCLUSION: PHQ-9 ≥10 substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies.

Microarchitecture of three-dimensional scaffolds influences cell migration behavior via junction interactions.

Cell migration plays a critical role in a wide variety of physiological and pathological phenomena as well as in scaffold-based tissue engineering. Cell migration behavior is known to be governed by biochemical stimuli and cellular interactions. Biophysical processes associated with interactions between the cell and its surrounding extracellular matrix may also play a significant role in regulating migration. Although biophysical properties of two-dimensional substrates have been shown to significantly influence cell migration, elucidating factors governing migration in a three-dimensional environment is a relatively new avenue of research. Here, we investigate the effect of the three-dimensional microstructure, specifically the pore size and Young's modulus, of collagen-glycosaminoglycan scaffolds on the migratory behavior of individual mouse fibroblasts. We observe that the fibroblast migration, characterized by motile fraction as well as locomotion speed, decreases as scaffold pore size increases across a range from 90 to 150 mum. Directly testing the effects of varying strut Young's modulus on cell motility showed a biphasic relationship between cell speed and strut modulus and also indicated that mechanical factors were not responsible for the observed effect of scaffold pore size on cell motility. Instead, in-depth analysis of cell locomotion paths revealed that the distribution of junction points between scaffold struts strongly modulates motility. Strut junction interactions affect local directional persistence as well as cell speed at and away from the junctions, providing a new biophysical mechanism for the governance of cell motility by the extracellular microstructure.

Characterization of mineralized collagen-glycosaminoglycan scaffolds for bone regeneration.

Mineralized collagen-glycosaminoglycan scaffolds designed for bone regeneration have been synthesized via triple co-precipitation in the absence of a titrant phase. Here, we characterize the microstructural and mechanical properties of these newly developed scaffolds with 50 and 75 wt.% mineral content. The 50 wt.% scaffold had an equiaxed pore structure with isotropic mechanical properties and a Ca-P-rich mineral phase comprised of brushite; the 75 wt.% scaffold had a bilayer structure with a pore size varying in the through-thickness direction and a mineral phase comprised of 67% brushite and 33 wt.% monetite. The compressive stress-strain response of the scaffolds was characteristic of low-density open-cell foams with distinct linear elastic, collapse plateau and densification regimes. The elastic modulus and strength of individual struts within the scaffolds were measured using an atomic force microscopy cantilevered beam-bending technique and compared with the composite response under indentation and unconfined compression. Cellular solids models, using the measured strut properties, overestimated the overall mechanical properties for the scaffolds; the discrepancy arises from defects such as disconnected pore walls within the scaffold. As the scaffold stiffness and strength decreased with increasing overall mineral content and were less than that of natural, mineralized collagen scaffolds, these microstructural/mechanical relations will be used to further improve scaffold design for bone regeneration applications.

A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.

BACKGROUND: Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse. METHODS: We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. RESULTS: Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). CONCLUSIONS: Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.

Mechanical characterization of collagen-glycosaminoglycan scaffolds.

Tissue engineering scaffolds are used extensively as three-dimensional analogs of the extracellular matrix (ECM). However, less attention has been paid to characterizing the scaffold microstructure and mechanical properties than to the processing and bioactivity of scaffolds. Collagen-glycosaminoglycan (CG) scaffolds have long been utilized as ECM analogs for the regeneration of skin and are currently being considered for the regeneration of nerve and conjunctiva. Recently a series of CG scaffolds with a uniform pore microstructure has been developed with a range of sizes of equiaxed pores. Experimental characterization and theoretical modeling techniques have previously been used to describe the pore microstructure, specific surface area, cell attachment and permeability of these variants. The results of tensile and compressive tests on these CG scaffolds and of bending tests on the individual struts that define the scaffold network are reported here. The CG scaffold variants exhibited stress-strain behavior characteristic of low-density, open-cell foams with distinct linear elastic, collapse plateau and densification regimes. Scaffolds with equiaxed pores were found to be mechanically isotropic. The independent effects of hydration level, pore size, crosslink density and relative density on the mechanical properties was determined. Independent control over scaffold stiffness and pore size was obtained. Good agreement was observed between experimental results of scaffold mechanical characterization and low-density, open-cell foam model predictions for uniform scaffolds. The characterized scaffold variants provide a standardized framework with defined extracellular environments (microstructure, mechanics) for in vitro studies of the mechanical interactions between cells and scaffolds as well as in vivo tissue engineering studies.

The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering.

The permeability of scaffolds and other three-dimensional constructs used for tissue engineering applications is important as it controls the diffusion of nutrients in and waste out of the scaffold as well as influencing the pressure fields within the construct. The objective of this study was to characterize the permeability/fluid mobility of collagen-GAG scaffolds as a function of pore size and compressive strain using both experimental and mathematical modeling techniques. Scaffolds containing four distinct mean pore sizes (151, 121, 110, 96 microns) were fabricated using a freeze-drying process. An experimental device was constructed to measure the permeability of the scaffold variants at different levels of compressive strain (0, 14, 29 and 40% while a low-density open-cell foam cellular solids model utilizing a tetrakaidecahedral unit cell was used to accurately model the permeability of each scaffold variant at all level of applied strain. The results of both the experimental and the mathematical analysis revealed that scaffold permeability increases with increasing pore size and decreases with increasing compressive strain. The excellent comparison between experimentally measured and predicted scaffold permeability suggests that cellular solids modelling techniques can be utilized to predict scaffold permeability under a variety of physiological loading conditions as well as to predict the permeability of future scaffolds with a wide variety of pore microstructures.

Lightweight 3D cellular composites inspired by balsa.

Additive manufacturing technologies offer new ways to fabricate cellular materials with composite cell walls, mimicking the structure and mechanical properties of woods. However, materials limitations and a lack of design tools have confined the usefulness of 3D printed cellular materials. We develop new carbon fiber reinforced, epoxy inks for 3D printing which result in printed materials with longitudinal Young's modulus up to 57 GPa (exceeding the longitudinal modulus of wood cell wall material). To guide the design of hierarchical cellular materials, we developed a parameterized, multi-scale, finite element model. Computational homogenization based on finite element simulations at multiple length scales is employed to obtain the elastic properties of the material at multiple length scales. Parameters affecting the elastic response of cellular composites, such as the volume fraction, orientation distribution, and aspect ratio of fibers within the cell walls as well as the cell geometry and relative density are included in the model. To validate the model, experiments are conducted on both solid carbon fiber/epoxy composites and cellular structures made from them, showing excellent agreement with computational multi-scale model predictions, both at the cell-wall and at the cellular-structure levels. Using the model, cellular structures are designed and experimentally shown to achieve a specific stiffness nearly as high as that observed in balsa wood. The good agreement between the multi-scale model predictions and experimental data provides confidence in the practical utility of this model as a tool for designing novel 3D cellular composites with unprecedented specific elastic properties.

Spatially-localized bench-top X-ray scattering reveals tissue-specific microfibril orientation in Moso bamboo.

BACKGROUND: Biological materials have a complex, hierarchical structure, with vital structural features present at all size scales, from the nanoscale to the macroscale. A method that can connect information at multiple length scales has great potential to reveal novel information. This article presents one such method with an application to the bamboo culm wall. Moso (Phyllostachys edulis) bamboo is a commercially important bamboo species. At the cellular level, bamboo culm wall consists of vascular bundles embedded in a parenchyma cell tissue matrix. The microfibril angle (MFA) in the bamboo cell wall is related to its macroscopic longitudinal stiffness and strength and can be determined at the nanoscale with wide-angle X-ray scattering (WAXS). Combining WAXS with X-ray microtomography (XMT) allows tissue-specific study of the bamboo culm without invasive chemical treatment. RESULTS: The scattering contribution of the fiber and parenchyma cells were separated with spatially-localized WAXS. The fiber component was dominated by a high degree of orientation corresponding to small MFAs (mean MFA 11°). The parenchyma component showed significantly lower degree of orientation with a maximum at larger angles (mean MFA 65°). The fiber ratio, the volume of cell wall in the fibers relative to the overall volume of cell wall, was determined by fitting the scattering intensities with these two components. The fiber ratio was also determined from the XMT data and similar fiber ratios were obtained from the two methods, one connected to the cellular level and one to the nanoscale. X-ray diffraction tomography was also done to study the differences in microfibril orientation between fibers and the parenchyma and further connect the microscale to the nanoscale. CONCLUSIONS: The spatially-localized WAXS yields biologically relevant, tissue-specific information. With the custom-made bench-top set-up presented, diffraction contrast information can be obtained from plant tissue (1) from regions-of-interest, (2) as a function of distance (line scan), or (3) with two-dimensional or three-dimensional tomography. This nanoscale information is connected to the cellular level features.

Is "Sexual Competence" at First Heterosexual Intercourse Associated With Subsequent Sexual Health Status?

The timing of first sexual intercourse is often defined in terms of chronological age, with particular focus on "early" first sex. Arguments can be made for a more nuanced concept of readiness and appropriateness of timing of first intercourse. Using data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), conducted in 2010-2012, this study examined whether a context-based measure of first intercourse-termed sexual competence-was associated with subsequent sexual health in a population-based sample of 17-to 24-year-olds residing in Britain (n = 2,784). Participants were classified as "sexually competent" at first intercourse if they reported the following four criteria: contraceptive protection, autonomy of decision (not due to external influences), that both partners were "equally willing," and that it happened at the "right time." A lack of sexual competence at first intercourse was independently associated with testing positive for human papillomavirus (HPV) at interview; low sexual function in the past year; and among women only, reported sexually transmitted infection (STI) diagnosis ever; unplanned pregnancy in the past year; and having ever experienced nonvolitional sex. These findings provide empirical support for defining the nature of first intercourse with reference to contextual aspects of the experience, as opposed to a sole focus on chronological age at occurrence.