A “Hired Girl” Testifies against the “Son of a Prominent Family”: Bastardy and Rape on the Nineteenth-Century Nebraska Plains

In Red Cloud, Nebraska, in 1887, Anna “Annie” Sadilek (later Pavelka) pressed bastardy charges against the “son of a prominent family,” even though she could have, according to her pretrial testimony, pressed charges for rape. To the literary world, Sadilek is better known as Ántonia Shimerda, the powerful protagonist in Willa Cather’s 1918 novel, My Ántonia. However, it is Sadilek’s real-life experience that allows us to better understand life on the Nebraska Plains, specifically through an examination of the state’s rape laws and the ways these laws were subsequently interpreted by the courts. The Nebraska Supreme Court, between 1877 and 1886, established the need for the state to prove force as a primary component of the definition for rape, drew boundaries around acceptable reporting times, and solidified their stance on the requirement of corroborating testimony. These factors led Sadilek to charge Charley Kaley not with rape but with bastardy, a civil suit, which almost guaranteed a successful outcome for Sadilek and her child because it would not burden the county or state with their financial welfare. In analyzing Sadilek’s choices before the law, this article demonstrates the complexities of the gendered legal systems facing women like Sadilek who sought justice for crimes of a sexual nature. Additionally significant, this article draws attention to a space and place that lacks significant study in regard to the sexual power dynamics of the nineteenth-century Great Plains West, a multicultural contact zone highly susceptible to the influences of hypermasculine control

Preparatory study for the revaluation of the EQ-5D tariff: methodology report.

BACKGROUND: EQ-5D is a widely used generic measure of health with a 'tariff', or preference weights, obtained from the general population, using time trade-off (TTO). PRET (Preparatory study for the Re-valuation of the EQ-5D Tariff project) contributes towards the methodology for its revaluation. METHODS: Stage 1 examined key assumptions typically involved in health-state valuations through a series of binary choice exercises, namely that health-state preferences are independent of (1) duration of the state; (2) whose health it is (i.e. perspective); (3) length of 'lead time' (a mechanism to value all states on the same scale, including those who are worse than being dead); (4) when health events take place (time preference); and (5) satisfaction associated with the state. Further topics addressed were (6) exhaustion of lead time in the worst state; (7) health-state valuation using discrete choice experiments (DCEs) with a duration attribute; and (8) binary choice administration of lead time - time trade-off (LT-TTO). Stage 1 consisted of an online survey with 6000 respondents. Stage 2 compared the results above to those of an identical survey conducted in 200 face-to-face computer-assisted personal interviews (CAPIs), covering topics (1) to (7). Stages 3 and 4 examined - in more detail and depth - issues taken from stage 1. Stage 3 consisted of CAPI surveys of a representative UK sample of 300, using examples of TTO, LT-TTO, and DCE with duration, each followed by extensive feedback questions. Stage 4 was a more intensive exercise involving a qualitative analysis of people's thought processes during both binary choice and iterative health-state valuation exercises. Data were collected through 'think-aloud' methods in 30 interviews of a convenience sample. RESULTS: Stage 1 found that health-state values are not independent of (1) duration of the state but there is no clear pattern; (2) whose health it is; (3) the duration of 'lead time' but there was no clear pattern; (4) when health events take place; or (5) satisfaction associated with the state. Furthermore, (6) exhaustion of lead time in the worst state was subject to substantial framing effects; (7) the five-level version of the EQ-5D (EQ-5D-5L) can be valued using DCE with duration as an attribute; and (8) binary choice LT-TTO can be administered in an online environment. Stage 2 found that although online surveys and CAPI surveys resulted in different compositions of respondents, at the aggregate, their responses to the experimental questions covering (1) to (7) above were not statistically significantly different from each other. Stages 3 and 4 found that TTO and LT-TTO were easier than DCE with duration; respondents did not necessarily trade across all attributes of EQ-5D; some respondents found it difficult to distinguish between the two worst levels of EQ-5D-5L, and some respondents may be thinking about the impact of their ill health on their family. CONCLUSIONS: In order for the National Institute for Health and Care Excellence to make the most appropriate decisions, the EQ-5D tariff needs to incorporate the latest understanding of health-state preferences. PRET contributed to the knowledge base on the conduct of health-state valuation studies. FUNDING: The Medical Research Council (MRC)-National Institute for Health Research (NIHR) Methodology Research Programme funded the PRET project (MRC ref. G0901500), and the EuroQol Group funded the PRET-AS project (Preparatory study for the Re-valuation of the EQ-5D Tariff project - Additional Sample) as an extension to the PRET project with formal agreement from the MRC

The RETRIEVE checklist for studies reporting the elicitation of stated preferences for child health-related quality of life

Background: Recent systematic reviews show varying methods for eliciting, modelling, and reporting preference-based values for child health-related quality-of-life (HRQoL) outcomes, thus producing value sets with different characteristics. Reporting in many of the reviewed studies was found to be incomplete and inconsistent, making them difficult to assess. Checklists can help to improve standards of reporting; however, existing checklists do not address methodological issues for valuing child HRQoL. Existing checklists also focus on reporting methods and processes used in developing HRQoL values, with less focus on reporting of the values’ key characteristics and properties. We aimed to develop a checklist for studies generating values for child HRQoL, including for disease-specific states and value sets for generic child HRQoL instruments. Development: A conceptual model provided a structure for grouping items into five modules. Potential items were sourced from an adult HRQoL checklist review, with additional items specific to children developed using recent reviews. Checklist items were reduced by eliminating duplication and overlap, then refined for relevance and clarity via an iterative process. Long and short checklist versions were produced for different user needs. The resulting long RETRIEVE contains 83 items, with modules for reporting methods (A–D) and characteristics of values (E), for researchers planning and reporting child health valuation studies. The short RETRIEVE contains 14 items for decision makers or researchers choosing value sets. Conclusion: Applying the RETRIEVE checklists to relevant studies suggests feasibility. RETRIEVE has the potential to improve completeness in the reporting of preference-based values for child HRQOL outcomes and to improve assessment of preference-based value sets

Using Age-Specific Values for Pediatric HRQoL in a Cost-Effectiveness Analysis : Is There a Problem to Be Solved? If So, How?

Value sets for the EQ-5D-Y-3L published to date appear to have distinctive characteristics compared with value sets for corresponding adult instruments: in many cases, the value for the worst health state is higher and there are fewer values < 0. The aim of this paper is to consider how and why values for child and adult health differ; and what the implications of that are for the use of EQ-5D-Y-3L values in economic evaluations to inform healthcare resource allocation decisions. We posit four potential explanations for the differences in values: (a) The wording of severity labels may mean the worst problems on the EQ-5D-Y-3L are descriptively less severe than those on the EQ-5D-5L; (b) Adults may genuinely consider that children are less badly affected than adults by descriptively similar health issues. That is, for any given health problem, adult respondents in valuation studies consider children’s overall health-related quality of life (HRQoL) on average to be higher than that for adults; (c) Values are being sought by eliciting adults’ stated preferences for HRQoL in another person, rather than in themselves (regardless of whether the ‘other person’ concerned is a child); and (d) The need to elicit preferences for child HRQoL that are anchored at dead = 0 invokes special considerations regarding children’s survival. Existing evidence does not rule out the possibility that (c) and (d) exert an upward bias in values. We consider the implications of that for the interpretation and use of values for pediatric HRQoL. Alternative methods for valuing children’s HRQoL in a manner that is not ‘age specific’ are possible and may help to avoid issues of non-comparability. Use of these methods would place the onus on health technology assessment bodies to reflect any special considerations regarding child quality-adjusted life-year gains

Estimating a preference-based single index measuring the quality of life impact of self-management for diabetes

Objective. Self-management is becoming increasingly important in diabetes but is neglected in conventional preference-based measures. The objective of this paper was to generate health state utility values for a novel classification system measuring the quality-of-life impact of self-management for diabetes, which can be used to generate quality-adjusted life years (QALYs). Methods. A large online survey was conducted using a discrete choice experiment (DCE), with duration as an additional attribute, on members of the UK general population (n = 1,493) to elicit values for health (social limitations, mood, vitality, hypoglycaemia) and non-health (stress, hassle, control, support) aspects of self-management in diabetes. The data were modelled using a conditional fixed-effects logit model and utility estimates were anchored on the one to zero (full health to dead) scale. Results. The model produced significant and consistent coefficients, with one logical inconsistency and 3 insignificant coefficients for the milder levels of some attributes. The anchored utilities ranged from 1 for the best state to −0.029 for the worst state (meaning worse than dead) defined by the classification system. Conclusion. The results presented here can potentially be used to generate utility values capturing the day to day impact of interventions in diabetes on both health and self-management. These utility values can potentially be used to generate QALYs for economic models of the cost-effectiveness of interventions in diabetes

Marine Ecoregion and Deepwater Horizon Oil Spill Affect Recruitment and Population Structure of a Salt Marsh Snail

Marine species with planktonic larvae often have high spatial and temporal variation in recruitment that leads to subsequent variation in the ecology of benthic adults. Using a combination of published and unpublished data, we compared the population structure of the salt marsh snail, Littoraria irrorata, between the South Atlantic Bight and the Gulf Coast of the United States to infer geographic differences in recruitment and to test the hypothesis that the Deepwater Horizon oil spill led to widespread recruitment failure of L. irrorata in Louisiana in 2010. Size-frequency distributions in both ecoregions were bimodal, with troughs in the distributions consistent with a transition from sub-adults to adults at ~13 mm in shell length as reported in the literature; however, adult snails reached larger sizes in the Gulf Coast. The ratio of sub-adults to adults was 1.5–2 times greater in the South Atlantic Bight than the Gulf Coast, consistent with higher recruitment rates in the South Atlantic Bight. Higher recruitment rates in the South Atlantic Bight could contribute to higher snail densities and reduced adult growth in this region. The ratio of sub-adults to adults in Louisiana was lower in 2011 than in previous years, and began to recover in 2012–2014, consistent with widespread recruitment failure in 2010, when large expanses of spilled oil were present in coastal waters. Our results reveal an important difference in the ecology of a key salt marsh invertebrate between the two ecoregions, and also suggest that the Deepwater Horizon oil spill may have caused widespread recruitment failure in this species and perhaps others with similar planktonic larval stages

What is the best approach to adopt for identifying the domains for a new measure of health, social care and carer-related quality of life to measure quality-adjusted life years? Application to the development of the EQ-HWB

Economic evaluation combines costs and benefits to support decision-making when assessing new interventions using preference-based measures to measure and value benefits in health or health-related quality of life. These health-focused instruments have limited ability to capture wider impacts on informal carers or outcomes in other sectors such as social care. Sector-specific instruments can be used but this is problematic when the impact of an intervention straddles different sectors.An alternative approach is to develop a generic preference-based measure that is sufficiently broad to capture important cross-sector outcomes. We consider the options for the selection of domains for a cross-sector generic measure including how to identify domains, who should provide information on the domains and how this should be framed. Beyond domain identification, considerations of criteria and stakeholder needs are also identified.This paper sets out the case for an approach that relies on the voice of patients, social care users and informal carers as the main source of domains and describes how the approach was operationalised in the ‘Extending the QALY’ project which developed the new measure, the EQ-HWB (EQ health and wellbeing instrument). We conclude by discussing the strengths and limitations of this approach. The new measure should be sufficiently generic to be used to consistently evaluate health and social care interventions, yet also sensitive enough to pick up important changes in quality of life in patients, social care users and carers

Common Genetic Variants, Acting Additively, Are a Major Source of Risk for Autism

Background: Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods: By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results: By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions: Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability

Common genetic variants, acting additively, are a major source of risk for autism

Abstract Background Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.http://deepblue.lib.umich.edu/bitstream/2027.42/112370/1/13229_2012_Article_55.pd

Nature vs. Nurture: Defining the Effects of Mesenchymal Stromal Cell Isolation and Culture Conditions on Resiliency to Palmitate Challenge

As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab has shown that palmitate, a saturated fatty acid elevated in the serum of patients with obesity, causes MSCs to convert from an immunosuppressive to an immunostimulatory state at moderate to high physiological levels. This demonstrated that metabolically-diseased environments, like obesity, alter the immunomodulatory efficacy of healthy donor MSCs. In addition, it highlighted the need to test MSC efficacy not only in ideal conditions, but within challenging metabolic environments. To determine how the choice of xeno- vs. xeno-free media during isolation and expansion would affect future immunosuppressive function, umbilical cord explants from seven donors were subdivided and cultured within xeno- (fetal bovine serum, FBS) or xeno-free (human platelet lysate, PLT) medias, creating 14 distinct MSC preparations. After isolation and primary expansion, umbilical cord MSCs (ucMSC) were evaluated according to the ISCT minimal criteria for MSCs. Following baseline characterization, ucMSC were exposed to physiological doses of palmitate and analyzed for metabolic health, apoptotic induction, and immunomodulatory potency in co-cultures with stimulated human peripheral blood mononuclear cells. The paired experimental design (each ucMSC donor grown in two distinct culture environments) allowed us to delineate the contribution of inherent (nature) vs. environmentally-driven (nurture) donor characteristics to the phenotypic response of ucMSC during palmitate exposure. Culturing MSCs in PLT-media led to more consistent growth characteristics during the isolation and expansion for all donors, resulting in faster doubling times and higher cell yields compared to FBS. Upon palmitate challenge, PLT-ucMSCs showed a higher susceptibility to palmitate-induced metabolic disturbance, but less susceptibility to palmitate-induced apoptosis. Most striking however, was that the PLT-ucMSCs resisted the conversion to an immunostimulatory phenotype better than their FBS counterparts. Interestingly, examining MSC suppression of PBMC proliferation at physiologic doses of palmitate magnified the differences between donors, highlighting the utility of evaluating MSC products in stress-based assays that reflect the challenges MSCs may encounter post-transplantation