Revising ethical guidance for the evaluation of programmes and interventions not initiated by researchers

Public health and service delivery programmes, interventions and policies (collectively, “programmes)” are typically developed and implemented for the primary purpose of effecting change rather than generating knowledge. Nonetheless, evaluations of these programmes may produce valuable learning that helps to determine effectiveness and costs as well as informing design and implementation of future programmes. Such studies might be termed “opportunistic evaluations”, since they are responsive to emergent opportunities rather than being studies of interventions that are initiated or designed by researchers. However, current ethical guidance and registration procedures make little allowance for scenarios where researchers have played no role in the development or implementation of a programme, but nevertheless plan to conduct a prospective evaluation. We explore the limitations of the guidance and procedures with respect to opportunistic evaluations, providing a number of examples. We propose that the key missing distinction in current guidance is that moral responsibility: researchers can only be held accountable for those aspects of a study over which they have control. We argue that requiring researchers to justify an intervention, programme or policy that would occur regardless of their involvement prevents or hinders research in the public interest without providing any further protections to research participants. We recommend that trial consent and ethics procedures allow for a clear separation of responsibilities for the intervention and the evaluation.SIW and RJL are funded by the NIHR Global Health Research Unit on Improving Health in Slums. CT, PJC and RJL are also supported by the National Institute for Health Research (NIHR) Collaboration for Leadership for Applied Health Research Care (CLAHRC) West Midlands initiative. EBW and ELD are employed by Partners In Health. MD-W is supported by the Health Foundation’s grant to the University of Cambridge for The Healthcare Improvement Studies (THIS) Institute. THIS Institute is supported by the Health Foundation - an independent charity committed to bringing about better health and health care for people in the UK. This work was also supported by MDW’s Wellcome Trust Investigator award WT09789. MDW is a National Institute for Health Research (NIHR) Senior Investigator. This paper presents independent research and the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Healt

Odontoid metastasis: a potential lethal complication

Nearly one third of cervical spine metastasis has a primary breast malignancy. Patients with cervical metastasis have higher mortality due to advanced stage of the malignancy. Treatment is palliative to relieve pain, prevent pathological fracture, improve mobility and function, and prolong survival. We describe a 40-year-old woman with a history of breast cancer who presented with neck and shoulder pain of 1 week duration with no neurological deficit. Following clinical examination, radiographs taken of the cervical spine was normal. Radiographs repeated 3 weeks later revealed a large lytic lesion of the odontoid occupying 70–80% of the peg. Further investigation including magnetic resonance imaging and bone scan showed no further spinal lesions. She underwent cyclical radiotherapy with complete resolution of the odontoid peg lesion and clinically was asymptomatic at 2 years. Metastatic lesions of the odontoid are atypical, and this case reinforces the necessity of early detection to evade disastrous consequences

Advancing the public health applications of Chlamydia trachomatis serology

© 2018 Elsevier Ltd Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications

Dolor posoperatorio en craneotomía

In the postoperative period, 47% to 75% of the patients report some degree of pain. This study aimed to evaluate pain in the pre and postoperative period of patients submitted to craniotomy. This prospective research was carried out at the neurosurgery unit of a large Brazilian hospital. For a quantitative evaluation of pain, the verbal numeric 0 - 10 rating scale was used. Forty patients with a mean age of 36 years were evaluated. In the preoperative period, 34 (85%) patients indicated headache as the main cause of pain. In the postoperative period, 37 (93%) patients complained of pain while three (7%) reported absence of pain. Pain peaks were observed on the 2nd postoperative day, when 12 (32%) of the patients reported severe pain and 10 (27%) moderate pain. Absence of severe pain occurred after the 8th postoperative day. It was concluded that protocols of analgesia in craniotomy are needed, such as training nurses to better evaluate and handle pain.En el periodo postoperatorio, entre el 47% y el 75% de los pacientes relatan algún grado de dolor. Los objetivos de este trabajo fueron evaluar el dolor en el pre y postoperatorio de pacientes sometidos a craneotomía. Este estudio prospectivo fue realizado en la unidad de neurocirugía del Hospital São Paulo, Brasil. Para una evaluación cuantitativa del dolor se utilizó la escala numérica verbal graduada de 0 a 10. Fueron evaluados 40 pacientes con edad mediana de 36 años. En el preoperatorio 34 (85%) pacientes, reportaran cefalea como la principal causa del dolor. En el postoperatorio, 37 (93%) pacientes se quejaron de dolor, mientras 3 (7%) pacientes indicaron ausencia de dolor. El pico de dolor fue observado en el segundo día postoperatorio, cuando 12 (32%) pacientes reportaron dolor grave y 10 (27%) moderado. La ausencia de dolor grave ocurrió después del 8º día postoperatorio. Se concluyó que son necesarios protocolos de analgesia en craneotomía, tales como el entrenamiento de enfermeros para mejor evaluar y manejar el dolor.No pós-operatório, 47 a 75% dos pacientes relatam algum grau de dor. O objetivo deste trabalho foi avaliar a dor no pré e pós-operatório de pacientes submetidos a craniotomia. Estudo prospectivo, realizado na unidade de neurocirurgia do Hospital São Paulo. Para avaliação quantitativa de dor, foi utilizada a escala numérica verbal, graduada de 0 a 10. Foram avaliados 40 pacientes, com idade mediana de 36 anos. No pré-operatório, 34 (85%) pacientes relataram cefaléia como a principal causa de dor. No pós-operatório, 37 (93%) pacientes queixaram-se de dor e 3 (7%) pacientes referiram ausência de dor. O pico da dor foi observado no 2º pós-operatório, quando 16 (40%) dos pacientes referiram dor intensa e 11 (28%) queixaram-se de dor moderada. Ausência de dor intensa ocorreu após 6º pós-operatório. Concluí-se que há necessidade de protocolos de analgesia em craniotomia, como treinamento para os enfermeiros para melhor avaliação e manejo da dor.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Collective emotions online and their influence on community life

E-communities, social groups interacting online, have recently become an object of interdisciplinary research. As with face-to-face meetings, Internet exchanges may not only include factual information but also emotional information - how participants feel about the subject discussed or other group members. Emotions are known to be important in affecting interaction partners in offline communication in many ways. Could emotions in Internet exchanges affect others and systematically influence quantitative and qualitative aspects of the trajectory of e-communities? The development of automatic sentiment analysis has made large scale emotion detection and analysis possible using text messages collected from the web. It is not clear if emotions in e-communities primarily derive from individual group members' personalities or if they result from intra-group interactions, and whether they influence group activities. We show the collective character of affective phenomena on a large scale as observed in 4 million posts downloaded from Blogs, Digg and BBC forums. To test whether the emotions of a community member may influence the emotions of others, posts were grouped into clusters of messages with similar emotional valences. The frequency of long clusters was much higher than it would be if emotions occurred at random. Distributions for cluster lengths can be explained by preferential processes because conditional probabilities for consecutive messages grow as a power law with cluster length. For BBC forum threads, average discussion lengths were higher for larger values of absolute average emotional valence in the first ten comments and the average amount of emotion in messages fell during discussions. Our results prove that collective emotional states can be created and modulated via Internet communication and that emotional expressiveness is the fuel that sustains some e-communities.Comment: 23 pages including Supporting Information, accepted to PLoS ON

High apex predator biomass on remote Pacific islands

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Coral Reefs 26 (2007): 47-51, doi:10.1007/s00338-006-0158-x.On coral reefs in Palmyra—a central Pacific atoll with limited fishing pressure—total fish biomass is 428 and 299% greater than on reefs in nearby Christmas and Fanning Islands. Large apex predators –groupers, sharks, snappers, and jacks larger than 50 cm in length- account for 56% of total fish biomass in Palmyra on average, but only 7% and 3% on Christmas and Fanning. These biomass proportions are remarkably similar to those previously reported for the remote and uninhabited Northwest Hawaiian Islands (NWHI) and densely populated Main Hawaiian Islands (MHI), although Palmyra’s reefs are dominated in biomass by sharks (44% of the total), whereas the NWHI by jacks (39%). Herbivorous fish biomass was also greater on Palmyra than on Christmas and Fanning (343% and 207%, respectively). These results and previous findings indicate that remote, uninhabited islands support high levels of consumers, and highlight the importance of healthy coral reef ecosystems as reference points for assessment of human impacts and establishment of restoration goals

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Deep diversification of an AAV capsid protein by machine learning.

Modern experimental technologies can assay large numbers of biological sequences, but engineered protein libraries rarely exceed the sequence diversity of natural protein families. Machine learning (ML) models trained directly on experimental data without biophysical modeling provide one route to accessing the full potential diversity of engineered proteins. Here we apply deep learning to design highly diverse adeno-associated virus 2 (AAV2) capsid protein variants that remain viable for packaging of a DNA payload. Focusing on a 28-amino acid segment, we generated 201,426 variants of the AAV2 wild-type (WT) sequence yielding 110,689 viable engineered capsids, 57,348 of which surpass the average diversity of natural AAV serotype sequences, with 12-29 mutations across this region. Even when trained on limited data, deep neural network models accurately predict capsid viability across diverse variants. This approach unlocks vast areas of functional but previously unreachable sequence space, with many potential applications for the generation of improved viral vectors and protein therapeutics