Designing Out Medical Error, WCDH Boston 2011

This talk is about using research and design to reduce medical errors. It doesn’t matter whether you deliver healthcare in the old-fashioned pathogenic way, or salutogenically, it all falls apart if systems and protocols let the patient down, and harm them.

The Ingenuity of Ageing

What can a remarkable community of 6,000 retired academics living on the campus of Tsinghua University, Beijing, tell us about strategies for ‘ageing well’ in societies around the world? The Ingenuity of Ageing tells the story of an experimental piece of design research carried out by Dr Yanki Lee, a research fellow in the Helen Hamlyn Centre for Design at the Royal College of Art, who spent a year in China investigating new approaches to design for ageing. Supported by a UK-China Fellowship of Excellence funded by the Department of Business, Innovation and Skills (BIS), Dr Yanki Lee’s post-Doctoral study combines the techniques of reflexive ethnography and action research in order to challenge conventional thinking about the designer as expert and propose an alternative, participatory model of social interaction and innovation through which the ingenuity of older people can be revealed.

Study of Alternate Pavement Designs, 1968

This report is submitted pursuant to a contract dated August 30, 1967, between the Iowa State Highway Commission and Howard, Needles, Tammen & Bergendoff, Consulting Engineers, in connection with studies determining (11,A) alternate pavement designs, and (11,B) criteria for geometric design studies. Included herein is that portion of the report covering Paragraph 11,A, comprising preparation of alternate type pavement designs (Portland Cement and Asphaltic Concrete) for the Cedar Valley Freeway and proposed US-518 from 1-80 to US-30. These alternate pavement designs consider quality and availability of aggregates, soil conditions and traffic information, to determine details and dimensions of pavement design. Comparative cost studies were prepared from alternate design data and recommendations as to pavement type are presented for Commission review.

CULTIVATING THE O-SHAPED ENGINEER

With roots in the realm of construction, products and the physical world, it is not surprising that design and engineering education is grounded within the paradigm of consumerism and growth, perpetuating an unsustainable system. With a primary sustainability focus on material improvements, students are rarely asked to question the context into which their designs will fit, or to explore how their designs can promote a different (more sustainable) future rather than just a less unsustainable one. While we remain within this economic paradigm, even the T-shaped designer, with a broad general knowledge and deep expertise in one specific area, at best has potential to reduce negative environmental impact rather than to create positive social and environmental benefit. As such, the T-shaped engineer is allowed little opportunity to creatively explore more sustainable alternatives using systems-level thinking. This paper explores how we can prepare the next generation of designers and engineers to maximise their inherent skills to address the most intractable global issues, currently considered outside of their traditional remit. It questions the notion of the T-shaped designer, and proposes instead the O-shaped designer whose primary concern is circular systems, worldviews, synergies and relationships. The paper examines some of the tools used in depth, explaining some unexpected but essential components. Through two case studies it will show how their application is generating sustainable innovation and delivering new O-Shaped calibre of design engineers, ready to rebuild the future.

Makespaces: From Redistributed Manufacturing to a Circular Economy

Redistributed manufacturing is an emerging concept which captures the anticipated reshoring and localisation of production from large scale mass manufacturing plants to smaller-scale localised, customisable production units, largely driven by new digital production technologies. Critically, community-based digital fabrication workshops, or makespaces, are anticipated to be one hothouse for this new era of localised production and as such are key to future sustainable design and manufacturing practices. In parallel, the concept of the circular economy conceptualises the move from a linear economy of take-make-waste to a closed loop system, through repair, remanufacturing, and recycling to ultimately extend the value of products and materials. Despite the clear interplay between redistributed manufacturing and circular economy, there is limited research exploring this relationship. In light of these interconnected developments, the aim of this paper is to explore the role of makespaces in contributing to a circular economy through redistributed manufacturing activities. This is achieved through six semi-structured interviews with thought leaders on these topics. The research findings identify barriers and opportunities to both circular economy and redistributed manufacturing, uncover overlaps between circular economy and redistributed manufacturing, and identify a range of future research directions that can support the coming together of these areas. The research contributes to a wider conversation on embedding circular practices within makespaces and their role in redistributed manufacturing.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Developing a Process to Create and Validate an Instrument Assessing Student Attainment of Competencies at an Intercultural University in Mexico

This study took place at one of the intercultural universities (IUs) of Mexico that serve primarily indigenous students. The IUs are pioneers in higher education despite their numerous challenges (Bertely, 1998; Dietz, 2008; Pineda & Landorf, 2010; Schmelkes, 2009). To overcome educational inequalities among their students (Ahuja, Berumen, Casillas, Crispín, Delgado et al., 2004; Schmelkes, 2009), the IUs have embraced performance-based assessment (PBA; Casillas & Santini, 2006). PBA allows a shared model of power and control related to learning and evaluation (Anderson, 1998). While conducting a review on PBA strategies of the IUs, the researcher did not find a PBA instrument with valid and reliable estimates. The purpose of this study was to develop a process to create a PBA instrument, an analytic general rubric, with acceptable validity and reliability estimates to assess students’ attainment of competencies in one of the IU’s majors, Intercultural Development Management. The Human Capabilities Approach (HCA) was the theoretical framework and a sequential mixed method (Creswell, 2003; Teddlie & Tashakkori, 2009) was the research design. IU participants created a rubric during two focus groups, and seven Spanish-speaking professors in Mexico and the US piloted using students’ research projects. The evidence that demonstrates the attainment of competencies at the IU is a complex set of actual, potential and/or desired performances or achievements, also conceptualized as “functional capabilities” (FCs; Walker, 2008), that can be used to develop a rubric. Results indicate that the rubric’s validity and reliability estimates reached acceptable estimates of 80% agreement, surpassing minimum requirements (Newman, Newman, & Newman, 2011). Implications for practice involve the use of PBA within a formative assessment framework, and dynamic inclusion of constituencies. Recommendations for further research include introducing this study’s instrument-development process to other IUs, conducting parallel mixed design studies exploring the intersection between HCA and assessment, and conducting a case study exploring assessment in intercultural settings. Education articulated through the HCA empowers students (Unterhalter & Brighouse, 2007; Walker, 2008). This study aimed to contribute to the quality of student learning assessment at the IUs by providing a participatory process to develop a PBA instrument.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.

Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus

Molecular modi. cation is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N`-(benzofuroxan-5-yl) methylene] benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological pro. le. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 mu g/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. (C) 2009 Elsevier Ltd. All rights reserved.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Experimental design for mixed models with application to population pharmacokinetic studies

experimental design, mixed model, random coefficient regression model, population pharmacokinetics, approximate design

Optimal design for dose finding studies on safety and efficacy

Magdeburg, Univ., Fak. für Mathematik, Diss., 2009

Nest-box design for the study of diurnal raptors and owls is still an overlooked point in ecological, evolutionary and conservation studies: a review

The use of artificial nest-boxes has led to significant progress in bird conservation and in our understanding of the functional and evolutionary ecology of free-ranging birds that exploit cavities for roosting and reproduction. Nest-boxes and their improved accessibility have made it easier to perform comparative and experimental field investigations. However, concerns about the generality and applicability of scientific studies involving birds breeding in nest-boxes have been raised because the occupants of boxes may differ from conspecifics occupying other nest sites. Here we review the existing evidence demonstrating the importance of nest-box design to individual life-history traits in three falcon (Falconiformes) and seven owl (Strigiformes) species, as well as the extent to which publications on these birds describe the characteristics of exploited artificial nest-boxes in their 'methods' sections. More than 60% of recent publications did not provide any details on nest-box design (e.g. size, shape, material), despite several calls >15 years ago to increase the reporting of such information. We exemplify and discuss how variation in nest-box characteristics can affect or confound conclusions from nest-box studies and conclude that it is of overall importance to present details of nest-box characteristics in scientific publications.

Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

Design of surface forces apparatus for tribology studies combined with nonlinear optical spectroscopy

We describe the design, calibration, and performance of surface forces apparatus with the capability of illumination of the contact interface for spectroscopic investigation using optical techniques. The apparatus can be placed in the path of a Nd-YAG laser for studies of the linear response or the second harmonic and sum-frequency generation from a material confined between the two surfaces. In addition to the standard fringes of equal chromatic order technique, which we have digitized for accurate and fast analysis, the distance of separation can be measured with a fiber-optic interferometer during spectroscopic measurements (2 Å resolution and 10 ms response time). The sample approach is accomplished through application of a motor drive, piezoelectric actuator, or electromagnetic lever deflection for variable degrees of range, sensitivity, and response time. To demonstrate the operation of the instrument, the stepwise expulsion of discrete layers of octamethylcyclotetrasiloxane from the contact is shown. Lateral forces may also be studied by using piezoelectric bimorphs to induce and direct the motion of one surface.