Did Kettlewell commit fraud? Re-examining the evidence

H.B.D. Kettlewell is famous for several investigations conducted in the early 1950s on the phenomenon of industrial melanism, which are widely regarded as the classic demonstration of natural selection. In a recent (2002) book-length popularization of this episode in the history of the science, science writer Judith Hooper draws attention to what she interprets as discrepancies in the results reported by Kettlewell in his first scientific papers on the subject. On the basis of correspondence among Kettlewell and his associates, a survey of scientific publications that mention outstanding questions surrounding the phenomenon, as well as interviews with his son, surviving colleagues, and scientists who have worked on industrial melanism, Hooper all but explicitly concludes that Kettlewell committed fraud. The following essay critically examines her evidence in support of this allegation, including her discussion of his character, the alleged motives, and whether fraud was even committed. None of Hooper’s arguments is found to withstand careful scrutiny. The concluding section draws several conclusions about how history of science should be depicted to the public

A mechanism for mode selection in melt band instabilities

The deformation of partially molten mantle in tectonic environments can lead to exotic structures, which potentially affect both melt and plate-boundary focussing. Examples of such structures are found in laboratory deformation experiments on partially molten rocks. Simple-shear and torsion experiments demonstrate the formation of concentrated melt bands at angles of around 20° to the shear plane. The melt bands form in the experiments with widths of a few to tens of microns, and a band spacing roughly an order of magnitude larger. Existing compaction theories, however, cannot predict this band width structure, let alone any mode selection, since they infer the fastest growing instability to occur for wavelengths or bands of vanishing width. Here, we propose that surface tension in the mixture, especially on a diffuse interface in the limit of sharp melt-fraction gradients, can mitigate the instability at vanishing wavelength and thus permit mode selection for finite-width bands. Indeed, the expected weak capillary forces on the diffuse interface lead to predicted mode selection at the melt-band widths observed in the experiments

Melt-band instabilities with two-phase damage

Deformation experiments on partially molten rocks in simple shear form melt bands at 20° to the shear plane instead of at the expected 45° principal compressive stress direction. These melt bands may play an important role in melt focusing in mid-ocean ridges. Such shallow bands are known to form for two-phase media under shear if strongly non-Newtonian power-law creep is employed for the solid phase, or anisotropy imposed. However laboratory experiments show that shallow bands occur regardless of creep mechanism, even in diffusion creep, which is nominally Newtonian. Here we propose that a couple of forms of two-phase damage allow for shallow melt bands even in diffusion creep

Physics of melt extraction from the mantle : speed and style

Funding: This research received funding from the European Research Council under Horizon 2020 research and innovation program grant agreement number 772255. The authors thank the Isaac Newton Institute for Mathematical Sciences for its hospitality during the programme Melt in the Mantle which was supported by EPSRC Grant Number EP/K032208/1.Melt extraction from the partially molten mantle is among the fundamental processes shaping the solid Earth today and over geological time. A diversity of properties and mechanisms contribute to the physics of melt extraction. We review progress of the past ∼25 years of research in this area, with a focus on understanding the speed and style of buoyancy-driven melt extraction. Observations of U-series disequilibria in young lavas and the surge of deglacial volcanism in Iceland suggest this speed is rapid compared to that predicted by the null hypothesis of diffuse porous flow. The discrepancy indicates that the style of extraction is channelized. We discuss how channelization is sensitive to mechanical and thermochemical properties and feedbacks, and to asthenospheric heterogeneity. We review the grain-scale physics that underpins these properties and hence determines the physical behavior at much larger scales. We then discuss how the speed of melt extraction is crucial to predicting the magmatic response to glacial and sea-level variations. Finally, we assess the frontier of current research and identify areas where significant advances are expected over the next 25 years. In particular, we highlight the coupling of melt extraction with more realistic models of mantle thermochemistry and rheological properties. This coupling will be crucial in understanding complex settings such as subduction zones. ▪ Mantle melt extraction shapes Earth today and over geological time. ▪ Observations, lab experiments, and theory indicate that melt ascends through the mantle at speeds ∼30 m/year by reactively channelized porous flow. ▪ Variations in sea level and glacial ice loading can cause significant changes in melt supply to submarine and subaerial volcanoes. ▪ Fluid-driven fracture is important in the lithosphere and, perhaps, in the mantle wedge of subduction zones, but remains a challenge to model.PreprintPeer reviewe

Fast magma ascent, revised estimates from the deglaciation of Iceland

Partial melting of asthenospheric mantle generates magma that supplies volcanic systems. The timescale of melt extraction from the mantle has been hotly debated. Microstructural measurements of permeability typically suggest relatively slow melt extraction (1 m/yr) whereas geochemical (Uranium-decay series) and geophysical observations suggest much faster melt extraction (100 m/yr). The deglaciation of Iceland triggered additional mantle melting and magma flux at the surface. The rapid response has been used to argue for relatively rapid melt extraction. However, this episode must, at least to some extent, be unrepresentative, because the rates of magma eruption at the surface increased about thirty-fold relative to the steady state. Our goal is to quantify this unrepresentativeness. We develop a one-dimensional, time-dependent and nonlinear (far from steady-state), model forced by the most recent, and best mapped, Icelandic deglaciation. We find that 30 m/yr is the best estimate of the steady-state maximum melt velocity. This is a factor of about 3 smaller than previously claimed, but still relatively fast. We translate these estimates to other mid-ocean ridges accounting for differences in passive and active upwelling and degree of melting. We find that fast melt extraction greater than about 10 m/yr prevails globally

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. Five hundred and thirty-seven patients were visited by mobile teams of doctors and nurses from the National Health Service National Prion Clinic within 5 days of notification of a suspected diagnosis of sporadic Creutzfeldt-Jakob disease, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100-day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. Two hundred and eighty (52.1%) patients were female and the median age was 67.2 (interquartile range 10.5) years. Median survival from initial assessment was 24 days (range 0-1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; Medical Research Council Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical disease phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for methionine homozygous compared with methionine-valine heterozygous; 95% confidence interval 3.02-14.68 for 30-day mortality). Of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation, respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sporadic Creutzfeldt-Jakob disease patients using clinical, imaging and genetic data routinely available in a specialist national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care

Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS):a population-based, retrospective cohort study

BACKGROUND: There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.METHODS: The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.FINDINGS: Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.INTERPRETATION: Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.FUNDING: Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.</p

Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS):a population-based, retrospective cohort study

BACKGROUND: There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.METHODS: The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.FINDINGS: Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.INTERPRETATION: Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.FUNDING: Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.</p

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general

Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon

In the last 6 years, following the first pathological description of presumed amyloid-beta (Aβ) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)—attributed to the transmission of Aβ seeds—have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA