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PurposeThis paper outlines how Design for Lean Six Sigma methods aided a medical device manufacturing company in developing a new strategic space management and approval process for its manufacturing site.Design/methodology/approachThe project demonstrates the application of the Design for Lean Six Sigma and structured Define, Measure, Analyse, Design, and Verify methodology in designing and implementing a process that enables the case study manufacturing site to improve its space utilisation and free up space.FindingsThe project was validated in one manufacturing department, and the Design for Lean Six Sigma methodology resulted in creating 15% new space for that area, with opportunities identified to free up 44.7% of the total manufacturing floor space and realise over €2.2 million cost savings as well as start to manufacture new products launched.Research limitations/implicationsThe manuscript highlights for the first time how the Design for Lean Six Sigma methodology can be utilised for space utilisation and can be leveraged by other manufacturers. The current study's limitations are that it is a single-site case study application. Future longitudinal case studies on Design for Lean Six Sigma application in more manufacturing space utilisation projects would be useful. This study has implications for identifying best practices for Design for Lean Six Sigma methodology application in the device industry, thus improving the state of the art for introducing new manufacturing lines.Originality/valueThis is the first published work to utilise Design for Lean Six Sigma methodology for space utilisation in a medical device company. This review will provide medical devices and other manufacturing organisations with recommendations on utilising Design for Lean Six Sigma and design for improved space utilisation to reduce costs.

Antibiotic resistance is a health and socioeconomic crisis recognized as a serious threat affecting humans worldwide. Overuse of antibiotics enhances the spread of multidrug-resistant bacteria, causing drug-resistant infections which can be difficult to treat. This resistance, mostly of the acquired type, is thus a major clinical issue. Acquired resistance can occur by horizontal transfer of genes between bacteria (community settings), by vertical transmission that can occur between mother and her offspring at birth and during lactation, or spontaneously due to antibiotic exposure. While there have been multiple studies about the horizontal transfer of antibiotic-resistance genes, not many studies have been conducted to study their vertical transmission. Vertical transmission is of importance as the early bacterial colonization of infants has an impact on their health and immune programming throughout life. This review discusses some possible mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains and addresses the knowledge gaps for further studies.

Although physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes. For replication, we combined genotype from whole genome sequencing with phenotypic data from 6715 GenoFit participants aged 18–83 years. Dual energy X-ray absorptiometry assessed whole body lean mass (WBLM) and appendicular lean mass (ALM), hand dynamometry determined grip strength and ELISA measured plasma CAF in a subgroup (n = 260). Follow-up analyses included eQTL analyses, carrier analyses, single-variant and gene-burden tests. rs2710873 (AGRN) and rs71608359 (PRSS12) associate with muscle mass and strength phenotypes, respectively, in the UKBB (p = 8.9 × 10−6 and p = 8.4 × 10−6) and GenoFit cohort (p = 0.019 and p = 0.014). rs2710873 and rs71608359 are eQTLs for AGRN and PRSS12, respectively, in ≥ three tissues. Compared to non-carriers, carriers of rs2710873 had 4.0% higher WBLM and ALM (both p p p = 0.034). AGRN and PRSS12 are associated with muscle strength and mass in single-variant analyses, while PRSS12 has further associations with muscle strength in gene-burden tests. Our findings provide novel evidence of the relevance of AGRN and PRSS12 to sarcopenia phenotypes and support existing physiological data illustrating the importance of the NMJ in maintaining muscle health during ageing.

Background Carriage of HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADA) in patients with Crohn’s Disease (CD) receiving anti-TNF therapy. The presence of ADA is not uniformly associated with anti-TNF therapy failure as patients with adequate trough drug concentrations, even where ADA are present, can maintain therapy response. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of anti-TNF therapy evaluated by drug persistence in routine clinical practice. Methods A multi-centre retrospective study of IBD patients treated with anti-TNF therapy was performed. HLA-DQA1*05 genotypes were generated for each included patient by imputation from whole genome sequence using HIBAG. Only outcome of first anti-TNF therapy received by patients was evaluated in this study. Study primary endpoint was anti-TNF therapy persistence, expressed as time to discontinuation of anti-TNF therapy, segregated by HLA-DQA1*05 allele genotype. Patients discontinuing anti-TNF therapy due to primary or secondary loss of response or due to side-effects were considered therapy failures. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR). Results 921 IBD patients were identified with 877 included in the study population. Baseline demographics for the entire cohort and segregated by HLA-DQA1*05 allele status are summarised in Figure 1. In the study population, 543 (62%) had no copy, 281 (32%) one copy and 53 (6%) two copies of HLA-DQA1*05 allele. Median time to anti-TNF therapy discontinuation in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared to patients with 1 or no copy at 700-days follow-up: 418 versus 513 versus 541 days respectively, p=0.007 (Figure 2) with similar results observed at 2000-days follow-up (p=0.04). In a multivariate regression, factors independently associated with time to anti-TNF therapy discontinuation included: carriage of HLA-DQA1*05 allele OR 1.2, p=0.02; male gender OR 1.6, p=4.2 x 10-5; CD phenotype OR 0.7, p=0.009; and anti-TNF therapy type (infliximab) OR 1.5, p=0.002. Concomitant immunomodulator use was not associated with time to anti-TNF therapy discontinuation in this model, OR 0.97, p=0.84. Conclusion Carriage of two HLA-DQA1*05 alleles is associated with a less favorable outcome of anti-TNF therapy with shorter time to therapy discontinuation. Carriage of one HLA-DQA1*05 allele is not associated with outcome of anti-TNF therapy. Assessing HLA-DQA1*05 genotype has value in routine clinical practice as HLA-DQA1*05 homozygotes are at increased risk of anti-TNF failure which should be a consideration in IBD therapy selection.

In arts-based-research, knowledge and meaning emerge from people's experiences of being in dynamic, ambiguous, intentional, and ethical relationships with each other and the arts. This case study draws on Launer's "7

For decades, polymers have offered a unique combination of low cost and high durability, and are the material of choice for a huge range of applications. In the current energy system, such polymers require the combustion of fossil resources to provide process heat and electricity for manufacture, and release emissions from embodied resources when incinerated. Polymers which are biodegradable or based on biological feedstock avoid some of this resource use, but in some cases have greater energy requirements than fossil polymer equivalents. This work compares life cycle greenhouse gas emissions for pairs of fossil- and biologically-based polymers under various UK electricity, heat and end-of-life treatment scenarios between 2019 and 2040. As specific emissions from electricity and heat supply reduce over the period, life cycle emissions of all polymers fall. Polylactic acid was found to already have lower emissions than polystyrene in most scenarios. Low-density polyethylene was found to have lower emissions than poly(butylene adipate‐co‐terephthalate) in all cases to 2040. Both bio-based high density polyethylene and bio-based polyethylene terephthalate were found to have lower emissions than their fossil equivalents at some point between 2019 and 2040, depending on energy and end-of-life scenarios. Identifying and acting on these crossover points offers a route to significant reductions in the emissions of polymers, and even suggests that polymers with net negative emissions can be manufactured by 2040, offering the possibility of greenhouse gas sequestration through polymers made from agricultural waste.

The association of the human microbiome with health outcomes has attracted much interest toward its therapeutic manipulation. The likelihood of modulating the human microbiome in early life is high and offers great potential to exert profound effects on human development since the early microbiota shows more flexibility compared to that of adults. The human microbiota, being similar to human genetics, can be transmitted from mother to infant, providing insights into early microbiota acquisition, subsequent development, and potential opportunities for intervention. Here, we review adaptations of the maternal microbiota during pregnancy, birth, and infancy, the acquisition and succession of early-life microbiota, and highlight recent efforts to elucidate mother-to-infant microbiota transmission. We further discuss how the mother-to-infant microbial transmission is shaped; and finally we address potential directions for future studies to promote our understanding within this field.

Potato (Solanum tuberosum) is an indispensable commodity, mainly cultivated by high-altitude mountain households, that sustains and supports the livelihood of an overwhelming 51% of the Bhutanese population. The popularity of potato cultivation among Bhutanese farmers can be attributed to the crop’s adaptability to a wide range of agroclimatic conditions such as a rainfed crop, high productivity, an assured market, and a reliable source of income for the farming families. We hypothesize that the changing climate would make the livelihood associated with potato cultivation in Bhutan more vulnerable. We tested this hypothesis to identify the sources of vulnerability of smallholder farming households using the Livelihood Vulnerability Index (LVI) and LVI-IPCC (Intergovernmental Panel on Climate Change) approaches in six potato growing districts of Bhutan: Bumthang, Chukha, Gasa, Mongar, Tashigang, and Wangdue. Primary data were generated through a semi structured sample survey of 240 households on the seven major livelihood components of sociodemographic profiles, livelihood strategies, social networks, health, food, water, natural disasters, and climate variability. The results showed that the LVI (range 0.302 to 0.375) and LVI-IPCC (range −0.005 to 0.030) differed significantly (p < 0.001) across the districts. The districts of Tashigang and Mongar were less vulnerable than the other four districts by the LVI approach, whereas Bumthang was also revealed to be less vulnerable using the LVI-IPCC approach. The degree of vulnerability in a district differed according to their level of exposure and adaptive capacity to the climate change impacts of the potato farming household. The results are expected to serve as empirical evidence for designing a future course of actions to mitigate the negative impacts.

The human gut microbiome harbors a diverse range of microbes that play a fundamental role in the health and well-being of their host. The early-life microbiome has a major influence on human development and long-term health. Perinatal factors such as maternal nutrition, antibiotic use, gestational age and mode of delivery influence the initial colonization, development, and function of the neonatal gut microbiome. The perturbed early-life gut microbiome predisposes infants to diseases in early and later life. Understanding how perinatal factors guide and shape the composition of the early-life microbiome is essential to improving infant health. The following review provides a synopsis of perinatal factors with the most decisive influences on initial microbial colonization of the infant gut.

Hoy en día vivimos en una ciudad con un gran caos vehicular, lo que genera también una importante escasez de estacionamientos, es por ello que el presente proyecto, plantea brindar una solución eficiente y automatizada para mejorar el alquiler de estacionamientos que ofrecen las empresas. En relación con la demanda, encontramos que la demanda potencial es de 1 305 370 personas, pero luego de entrevistar a nuestros posibles socios comerciales obtendríamos 1 120 espacios en el 2026 para atender a nuestros clientes. El proyecto está enfocado a desarrollarse en Lima Metropolitana. Se eligió el distrito de San Isidro para ubicar las oficinas ya que favorece la cercanía a los socios comerciales. Encontramos que el recurso limitante serán los espacios de estacionamiento, ya que los 626 espacios en el primer año del proyecto no serán suficientes para atender a los 503 228 clientes de demanda que tendremos el primer año. Por otro lado, se necesitará vender 89 728 horas por mes o 1 076 736 horas por año para alcanzar un punto de equilibrio, lo que significa que cada espacio debe ser ocupado aproximadamente 141,97 horas por mes. El desarrollo de la aplicación es tercerizado ya que no es el enfoque de la empresa. El proveedor del desarrollo de la aplicación se va a encargar también del mantenimiento y soporte de esta. Se encontró que el proyecto es viable económica y financieramente, ya que se determinó que los indicadores están dentro de los niveles aceptados. En cuanto a indicadores sociales, se obtuvo que se debe invertir 47 324 soles al año para crear 1 puesto de trabajo debido a que el proyecto no requiere de gran cantidad de personal por el modelo de negocio establecido. También se pudo encontrar que se requiere S/ 0,13 de capital para obtener 1 punto de valor agregado. Finalmente, se halló que Se genera 7,5 de valor agregado por cada S/ 1,00 invertido. Nowadays we live in a city with great vehicular chaos, which also generates a lack of places to park, that is why the present Project brings an efficient and automatized solution to improve parking in parking slots. For the demand, we found that our potential demand is 1 241 400 persons, but after interviewing our potential business partners we will get 1 220 available slots to work with in 2026. The project is oriented to be developed in Lima Metropolitana. Specifically, in San Borja, San Isidro, Miraflores, Surco and San Miguel districts for socioeconomic and supply and demand reasons. San Isidro is the chosen district to our office location because it offers nearness to our business partners. We found that the limitant resource will be the parking slots, because the 626 parking slots in the first year of the project will not be enough to serve the 503 228 customers demand for the first year. On the other side, we will need to sell 89 728 hours per month or 1 076 736 hours per year to reach the balance point, which means that each slot has to be used 141,97 hours per month. The mobile app development is outsourced since it is not the company’s main focus. The app development provider is going to be in charge of the maintenance and technical support of it. We found that the project is economic and financially viable, because the KPI’s are in acceptable levels. About the social indicators, we got that we must invest 47 324 soles a year to create 1 work position for the reason our project and business model does not require a big workforce. We could also find that we require S/ 0,13 of capital to generate 1 value added point. Finally, we found that for every S/ 1 invested, it generates 7,5 value added points.

We analysed the human milk microbiome in a cohort of 80 lactating women and followed the dynamics in taxa over the course of lactation from birth to 6 months. Two hundred and thirty one milk samples were collected from full-term lactating women at 1, 4, 8 and 24 weeks following birth and analysed for microbiota composition using 16S rRNA sequencing. A significant decrease in milk microbiota diversity was observed throughout the first 6 months of lactation, with the greatest difference seen between week 8 and week 24. Nine genera predominated in milk over lactation from week 1 to week 24, comprising of Staphylococcus, Streptococcus, Pseudomonas, Acinetobacter, Bifidobacterium, Mesorhizobium, Brevundimonas, Flavobacterium, and Rhodococcus; however, fluctuations in these core genera were apparent over time. There was a significant effect of stage of lactation on the microbiome, while no effect of birth mode, infant sex and maternal BMI was observed throughout lactation. Streptococcus had the highest mean relative abundance at week 1 and 24 (17.3% and 24% respectively), whereas Pseudomonas predominated at week 4 (22%) and week 8 (19%). Bifidobacterium and Lactobacillus had the highest mean relative abundance at week 4 (5% and 1.4% respectively), and occurred at a relative abundance of ≤ 1% at all other time points. A decrease in milk microbiota diversity throughout lactation was also observed. This study concluded that lactation stage was the primary driving factor in milk microbiota compositional changes over lactation from birth to 6 months, while mode of delivery was not a factor driving compositional changes throughout human lactation.