Intersex in the Age of Queer Bioethics: Recommendations on the Fundamentals of Ovotestes Interventions for Intersex Youth

Queer Bioethics and the inventory of its potential populations include a wide range of queer subjects: lesbian parents, HIV-positive gay and bisexuals, transgender youth, and non-cisgendered individuals, to name a few. With the ethical dilemmas and ethical duties couched inside of a Queer Bioethics in mind, this article will consider one of the field’s most enduring citizens: the intersex child. More specifically, the figure of the intersex child with ovotesticular non-normativity will be scrutinized on ethical and clinical planes – a major aspect of queer bioethics is, after all, clinical ethics for queer populations. Ovotesticular conditions will be covered at length; we discuss different variations in addition to narrowing the topic to those with 46,XX and ambiguous genitalia, specifically those 75% diagnosed under the age of 20, and speak on issues related to this population. We will also briefly discuss the population of the 20% diagnosed under the age of 5 years old. Interventions will be discussed in all realms of intersex conditions – specifically ovotestes. We will conclude with a principalist approach to ethical topics such as autonomy, beneficence, and non-maleficence, weighing these principles equally and ultimately erring on the side of autonomy within pediatric ethics where possible.Queer-bioeettistä tarkastelua voi soveltaa joukkoon erilaisia queer-positioita: esimerkiksi lesbovanhempiin, HIV-positiivisiin homo- ja bi-miehiin, transsukupuolisiin nuoriin ja sukupuoleltaan moninaisiin henkilöihin. Tässä artikkelissa tarkastelemme intersukupuolisen lapsen positioita eettisten ongelmien ja velvollisuuksien keskiössä queer-bioeettisesti orientoituneesta näkökulmasta. Intersukupuolisuuden muodoista keskitymme ovotestikulaariseen epänormatiivisuuteen, jota käsittelemme sekä eettisellä että kliinisellä tasolla – onhan eräs queer-bioetiikan tarkoituksista luoda queer-väestöt kattavaa eettistä ohjeistusta lääketieteen kliiniseen työhön. Aluksi tarkastelemme ovotestikulaarisuuden eri muotoja. Seuraavaksi keskitymme intersukupuolisuuden 46,XX-muotoihin, joissa henkilön sukupuoli on ulkoisten sukuelinten perusteella epäselvä. Keskitymme erityisesti kysymyksiin, jotka koskevat 75 % intersukupuolisista henkilöistä, jotka saavat diagnoosin alle kaksikymmentävuotiaina. Sivuamme myös ongelmia, jotka koskevat sitä 20 % henkilöistä, jotka diagnosoidaan viisivuotiaana. Tarkastelemme intersukupuolisuuteen – ja erityisesti ovotestikulaarisuuteen – liittyviä käytänteitä. Lopuksi esitämme autonomian, hyvän tekemisen ja pahan tekemisen periaatteisiin nojaavan eettisen tarkastelun mallin sekä punnitsemme näitä periaatteita suhteessa intersukupuolisuuden kliiniseen hoitotyöhön. Päädymme suosittamaan autonomiaa lastenlääketieteen etiikan ohjenuoraksi silloin, kun se on mahdollista

A National Action Plan for Promoting Preconception Health and Health Care in the United States (2012–2014)

Preconception health and health care (PCHHC) has gained increasing popularity as a key prevention strategy for improving outcomes for women and infants, both domestically and internationally. The Action Plan for the National Initiative on Preconception Health and Health Care: A Report of the PCHHC Steering Committee (2012–2014) provides a model that states, communities, public, and private organizations can use to help guide strategic planning for promoting preconception care projects. Since 2005, a national public–private PCHHC initiative has worked to create and implement recommendations on this topic. Leadership and funding from the Centers for Disease Control and Prevention combined with the commitment of maternal and child health leaders across the country brought together key partners from the public and private sector to provide expertise and technical assistance to develop an updated national action plan for the PCHHC Initiative. Key activities for this process included the identification of goals, objectives, strategies, actions, and anticipated timelines for the five work-groups that were established as part of the original PCHHC Initiative. These are further described in the action plan. To assist other groups doing similar work, this article discusses the approach members of the PCHHC Initiative took to convene local, state, and national leaders to enhance the implementation of preconception care nationally through accomplishments, lessons learned, and projections for future directions

Clinical practice guideline monitoring children and young people with, or at risk of developing autosomal dominant polycystic kidney disease (ADPKD).

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is thought to affect about 1 in 1000 people in the UK. ADPKD causes a progressive decline in kidney function, with kidney failure tending to occur in middle age. Children and young people with ADPKD may not have any symptoms. However they may have high blood pressure, which may accelerate progression to later stages of chronic kidney disease.There is uncertainty and variation in how health professionals manage children and young people with confirmed or a family history of ADPKD, because of a lack of evidence. For example, health professionals may be unsure about when to test children's blood pressure and how often to monitor it in the hospital clinic or at the GP. They may have different approaches in recommending scanning or genetic testing for ADPKD in childhood, with some recommending waiting until the young person is mature enough to make this decision his or herself.This guideline is intended to help families affected by ADPKD by making sure that: health professionals with specialist knowledge in ADPKD offer you information on inheritance and potential benefits and harms of testing for ADPKD. the decision to test and the method of testing for ADPKD in children and young people is shared between you or your family and the health professionals blood pressure assessment is undertaken regularly in children and young people at risk of developing ADPKD

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Helminth burden and ecological factors associated with alterations in wild host gastrointestinal microbiota

Infection by gastrointestinal helminths of humans, livestock and wild animals is common, but the impact of such endoparasites on wild hosts and their gut microbiota represents an important overlooked component of population dynamics. Wild host gut microbiota and endoparasites occupy the same physical niche spaces with both affecting host nutrition and health. However, associations between the two are poorly understood. Here we used the commonly parasitized European shag (Phalacrocorax aristotelis) as a model wild host. Forty live adults from the same colony were sampled. Endoscopy was employed to quantify helminth infection in situ. Microbiota from the significantly distinct proventriculus (site of infection), cloacal and faecal gastrointestinal tract microbiomes were characterised using 16S rRNA gene-targeted high-throughput sequencing. We found increasingly strong associations between helminth infection and microbiota composition progressing away from the site of infection, observing a pronounced dysbiosis in microbiota when samples were partitioned into high- and low-burden groups. We posit this dysbiosis is predominately explained by helminths inducing an anti-inflammatory environment in the proventriculus, diverting host immune responses away from themselves. This study, within live wild animals, provides a vital foundation to better understand the mechanisms that underpin the three-way relationship between helminths, microbiota and hosts

Pattern of Relapse and Treatment Response in WNT- Activated Medulloblastoma

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention