Nurturing Societal Values in and Through Health Innovations; Comment on “What Health System Challenges Should Responsible Innovation in Health Address?”

Aligning innovation processes in healthcare with health system demands is a societal objective, not always achieved. In line with earlier contributions, Lehoux et al outline priorities for research, public communication, and policy action to achieve this objective. We endorse setting these priorities, while also highlighting a ‘commitment gap’ in collectively addressing system-level challenges. To acknowledge that stakeholders engaged in dialogue with one another are addressing the commitment gap is not a small step but a giant leap towards realising a socially responsible innovation agenda. Translating system-level demand signals into innovation opportunities is, therefore, the task-cum-art of all stakeholders, one that often prompts them to innovate how they deal with innovations

MSY Breakpoint Mapper, a database of sequence-tagged sites useful in defining naturally occurring deletions in the human Y chromosome

Y chromosome deletions arise frequently in human populations, where they cause sex reversal and Turner syndrome and predispose individuals to infertility and germ cell cancer. Knowledge of the nucleotide sequence of the male-specific region of the Y chromosome (MSY) makes it possible to precisely demarcate such deletions and the repertoires of genes lost, offering insights into mechanisms of deletion and the molecular etiologies of associated phenotypes. Such deletion mapping is usually conducted using polymerase chain reaction (PCR) assays for the presence or absence of a series of Y-chromosomal DNA markers, or sequence-tagged sites (STSs). In the course of mapping intact and aberrant Y chromosomes during the past two decades, we and our colleagues have developed robust PCR assays for 1287 Y-specific STSs. These PCR assays amplify 1698 loci at an average spacing of <14 kb across the MSY euchromatin. To facilitate mapping of deletions, we have compiled a database of these STSs, MSY Breakpoint Mapper (http://breakpointmapper.wi.mit.edu/). When queried, this online database provides regionally targeted catalogs of STSs and nearby genes. MSY Breakpoint Mapper is useful for efficiently and systematically defining the breakpoint(s) of virtually any naturally occurring Y chromosome deletion.National Institutes of Health (U.S.)Howard Hughes Medical Institut

The importance of genetic parenthood for infertile men and women

STUDY QUESTION: Do men and women beginning to attend a fertility clinic prefer genetic over non-genetic parenthood? SUMMARY ANSWER: Nearly, all infertile men and women prefer genetic parenthood. WHAT IS KNOWN ALREADY: Clinicians assume that all infertile couples prefer genetic parenthood over non-genetic parenthood and, therefore, consider treatments with donor gametes an option of last resort. Previous studies of the desire for parenthood identified 30 motivations for genetic parenthood, and 51 motivations for which having a genetically related child is not strictly necessary but might be deemed required. The exact strength of the preference of infertile men and women for genetic parenthood remains unclear, as does the importance of the various motivations. STUDY DESIGN, SIZE, DURATION: A questionnaire was developed based on a literature review. It was assessed by professionals and pilot tested among patients. The coded paper-pencil questionnaire was disseminated among both partners of 201 heterosexual infertile couples after their first consultation at one of two Belgian fertility clinics between October 2015 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey addressed: (i) the preference for genetic parenthood for themselves and for their partner, (ii) the importance of 30 motivations for genetic parenthood and (iii) the importance of 51 other motivations for parenthood and whether these motivations require being the genetic parent of their child to be fulfilled. To simplify presentation of the results, all 81 motivations were grouped into reliable categories of motivations using psychometric analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The survey was completed by 104 women and 91 men (response rate: 49%). Almost all respondents (98%) favored genetic over non-genetic parenthood for both their partner and themselves. One-third of the respondents stated they only wanted to parent their own genetically related child. Achieving genetic parenthood for their partner was considered significantly more important than achieving genetic parenthood for themselves. Within couples, men had a stronger preference for genetic parenthood (P = 0.004), but this was not significant after correction for educational level, which was significantly associated with the preference of both men and women. The 30 motivations for becoming a genetic parent clustered into 11 categories of which 'to experience a natural process' was deemed most important. The 51 motivations for becoming a parent for which having a genetically related child is not strictly necessary clustered into 14 categories of which 'to contribute to a child's well-being' and 'to experience the love of a child' were most important. Respondents deemed they would need to be the genetic parent of their child to fulfill nearly all their motivations for parenthood. LIMITATIONS REASONS FOR CAUTION: We included couples that visited the fertility clinic for the first time, and the preference for genetic parenthood might change throughout a fertility treatment trajectory. Moreover, what prospective parents expect to be important for their future well-being might not really define parents' well-being. WIDER IMPLICATIONS OF THE FINDINGS: The presumed preference of couples for genetic parenthood was confirmed. Resistance against using donor gametes is more likely among lower educated individuals. Researching whether non-genetic parents actually feel they cannot fulfill the 51 motivations for parenthood, could be a basis for developing patient informatio

Merck Animal Health Uses Operations Research Methods to Transform Biomanufacturing Productivity for Lifesaving Medicines

Merck Animal Health offers veterinarians, farmers, pet owners, and governments a wide range of veterinary pharmaceuticals, vaccines, health management solutions and services, and an extensive suite of connected technology that includes identification, traceability, and monitoring products. Biomanufacturing uses living organisms (i.e., viruses and bacteria) to grow the active ingredients in vaccines, pharmaceuticals, and therapeutics. This high-tech manufacturing process generates unique challenges not found in many other industries. For example, biomanufacturing operations include high levels of uncertainty and batch-to-batch variability in production yield, lead times, and costs. Additionally, the high cost of equipment and labor-intensive nature of operations preclude the ability to flexibly add capacity. Facing these challenges, we decided that harnessing the power of operations research and advanced analytics to complement our rich life sciences and biomanufacturing expertise was critical. After four years of collaboration with the Eindhoven University of Technology, we developed a portfolio of optimization models and decision support applications that substantially improved our biomanufacturing effectiveness. The implementation of the developed models had a significant impact by generating $200 million of additional revenue without the need for additional raw materials, energy resources, or new equipment. The developed models are widely adopted across the firm, thus enhancing its core function

An evolutionary perspective on Y-chromosomal variation and male infertility

Genetic variation on the Y chromosome is one of the best-documented causes of male infertility, but the genes responsible have still not been identified. This review discusses how an evolutionary perspective may help with interpretation of the data available and suggest novel approaches to identify key genes. Comparison with the chimpanzee Y chromosome indicates that USP9Y is dispensable in apes, but that multiple copies of TSPY1 may have an important role. Comparisons between infertile and control groups in search of genetic susceptibility factors are more complex for the Y chromosome than for the rest of the genome because of population stratification and require unusual levels of confirmation. But the extreme population stratification exhibited by the Y also allows populations particularly suitable for some studies to be identified, such as the partial AZFc deletions common in Northern European populations where further dissection of this complex structural region would be facilitated

The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility

BACKGROUND: The three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction. METHODS: In this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities. RESULTS: Intrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome. CONCLUSIONS: AZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome