Rate of re-infection of tissue culture-derived Latin American and East and Southern African cassava genotypes by mosaic disease

The rate of reinfection by cassava mosaic disease (CMD) in initially virus-free cassava plants of two Latin American and twelve East and Southern African cassava genotypes grown was studied under high disease pressure conditions. An improved clone, TMS 4(2)1425, from the International Institute of Tropical Agriculture was used as check. The virus-free plants had been produced through meristem-tip culture and multiplied in a pest-proof screen house. The genotypes were planted in single row plots of 5 plants each, arranged in a randomized complete block design with 4 replications and spacing of 1 × 1 m2. Incidence and severity of CMD on the genotypes were assessed weekly, from 4 to 16 weeks after planting (WAP). Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) tests for the cassava mosaic virus were carried out using young leaves collected randomly at 15, 16 and 17 WAP from plants both with and without symptoms. Six genotypes had > 60% CMD incidence at 4 WAP; by 7 WAP, 12 genotypes had > 60% incidence. Only Kigoma red, Kiroba, and UKG-41-6 were notinfected at 4 WAP while Mbudumali had 90% incidence at this time. At 16 WAP, ten genotypes had 100% CMD incidence; Kigoma Red was 39.6% infected. ELISA detected a mean CMD reinfection rate of 66.6%; PCR detected 69%. A high negative and significant (P< 0.01) correlation (r = - 0.70) was established between CMD severity and storage root yield.Keywords: Virus-free cassava genotypes, tissue culture, rate of reinfection, cassava mosaic diseas

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

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

The pathology of familial breast cancer: The pre-BRCA1/BRCA2 era - historical perspectives

A proportion of breast carcinomas develop as a result of a genetic predispostion to the disease. Prior to cloning of the BRCA1 and BRCA2 genes a limited number of studies were carried out to identify specific histopathological characteristics of hereditary breast cancer. These studies are the subject of this review. The main finding was the association of the (atypical) medullary type of breast cancer with a family history; the most important caveat being that medullary breast cancer is found more frequently in young patients. In view of the frequent bilateral occurrence of lobular cancer, this histologic type is also likely to be associated with a predisposing genetic defect. Future investigations will have to test this hypothesis. In addition to mutations in the BRCA1 and BRCA2 genes, there are as yet unidentified genetic defects predisposing to breast cancer development, and histopathology may well help in identifying these genes in the future

A real-time, quantitative PCR method using hydrolysis probes for the monitoring of Plasmodium falciparum load in experimentally infected human volunteers

Background: The accurate quantification of Plasmodium falciparum parasite numbers by PCR is an important tool for monitoring growth kinetics in subjects infected and subsequently treated with anti-malarial agents

Earlier Physical Therapy Input is Associated with a Reduced Length of Hospital Stay and Reduced Care Needs on Discharge in Frail Older Inpatients: An Observational Study

$\textbf{Background and Purpose}$: Pressures on hospital bed occupancy in the English National Health Service (NHS) have focused attention on enhanced service delivery models and methods by which physical therapists might contribute to effective cost savings, while retaining a patient-centered approach. Earlier access to physical therapy may lead to better outcomes in frail older inpatients, but this has not been well studied in acute NHS hospitals. Our aim was to retrospectively study the associations between early physical therapy input and length of hospital stay (LOS), functional outcomes and care needs on discharge. $\textbf{Methods}$: This was a retrospective observational study in a large tertiary university NHS hospital in the United Kingdom. We analyzed all admission episodes of people admitted to the Department of Medicine for the Elderly wards over 3 months in 2016. Patients were categorized into 2 groups: those examined by a physical therapist within 24 hours of admission and those examined after 24 hours of admission. The outcome variables were: LOS (days), functional measures on discharge (Elderly Mobility Scale and walking speed over 6 meters), and the requirement of formal care on discharge. Characterization variables on admission were: age, gender, existence of a formal care package, pre-admission abode, the Clinical Frailty Scale, Charlson Comorbidity Index, the Emergency Department Modified Early Warning Score, C-reactive protein level on admission, and the 4-item version of the Abbreviated Mental Test. The association between the delay to physical therapy input and LOS before discharge home was evaluated using a Cox proportional hazards regression model. $\textbf{Results and Discussion}$: There were 1022 hospital episodes over the study period. We excluded 19 who were discharged without being examined by a physical therapist. Of the remaining 1003, 584 (58.2%) were examined within 24 hours of admission (early assessment), and 419 (41.8%) after 24 hours of admission (late assessment). The median (interquartile range: IQR) LOS of the early assessment group was 6.7 (3.1–13.7) versus 10.0 (4.2-20.1) days in the late assessment group, P < 0.001. The early assessment group was less likely to require formal care on discharge: n=110 (20.3%) versus n=105 (27.0%), P = 0.016. No other statistically significant differences were seen between the 2 groups. In the unadjusted Cox proportional hazards model, the hazard ratio for early assessment compared to late assessment was 1.29 (95% confidence interval: 1.12-1.48, P < 0.001). Early assessment was associated with a 29% higher probability of discharge to usual residence within the first 21 days after admission, compared to late assessment. Adjustment for possible confounding variables increased the hazard ratio: 1.34 (1.16 – 1.55) P < 0.001. $\textbf{Conclusions}$: Early physical therapy input was associated with a shorter LOS and lower odds of needing care on discharge. This may be due to the beneficial effect of early physical therapy in preventing hospital-related deconditioning in frail older adults. However, causality cannot be inferred and further research is needed to investigate causal mechanisms

Earlier Physical Therapy Input is Associated with a Reduced Length of Hospital Stay and Reduced Care Needs on Discharge in Frail Older Inpatients: An Observational Study

$\textbf{Background and Purpose}$: Pressures on hospital bed occupancy in the English National Health Service (NHS) have focused attention on enhanced service delivery models and methods by which physical therapists might contribute to effective cost savings, while retaining a patient-centered approach. Earlier access to physical therapy may lead to better outcomes in frail older inpatients, but this has not been well studied in acute NHS hospitals. Our aim was to retrospectively study the associations between early physical therapy input and length of hospital stay (LOS), functional outcomes and care needs on discharge. $\textbf{Methods}$: This was a retrospective observational study in a large tertiary university NHS hospital in the United Kingdom. We analyzed all admission episodes of people admitted to the Department of Medicine for the Elderly wards over 3 months in 2016. Patients were categorized into 2 groups: those examined by a physical therapist within 24 hours of admission and those examined after 24 hours of admission. The outcome variables were: LOS (days), functional measures on discharge (Elderly Mobility Scale and walking speed over 6 meters), and the requirement of formal care on discharge. Characterization variables on admission were: age, gender, existence of a formal care package, pre-admission abode, the Clinical Frailty Scale, Charlson Comorbidity Index, the Emergency Department Modified Early Warning Score, C-reactive protein level on admission, and the 4-item version of the Abbreviated Mental Test. The association between the delay to physical therapy input and LOS before discharge home was evaluated using a Cox proportional hazards regression model. $\textbf{Results and Discussion}$: There were 1022 hospital episodes over the study period. We excluded 19 who were discharged without being examined by a physical therapist. Of the remaining 1003, 584 (58.2%) were examined within 24 hours of admission (early assessment), and 419 (41.8%) after 24 hours of admission (late assessment). The median (interquartile range: IQR) LOS of the early assessment group was 6.7 (3.1–13.7) versus 10.0 (4.2-20.1) days in the late assessment group, P < 0.001. The early assessment group was less likely to require formal care on discharge: n=110 (20.3%) versus n=105 (27.0%), P = 0.016. No other statistically significant differences were seen between the 2 groups. In the unadjusted Cox proportional hazards model, the hazard ratio for early assessment compared to late assessment was 1.29 (95% confidence interval: 1.12-1.48, P < 0.001). Early assessment was associated with a 29% higher probability of discharge to usual residence within the first 21 days after admission, compared to late assessment. Adjustment for possible confounding variables increased the hazard ratio: 1.34 (1.16 – 1.55) P < 0.001. $\textbf{Conclusions}$: Early physical therapy input was associated with a shorter LOS and lower odds of needing care on discharge. This may be due to the beneficial effect of early physical therapy in preventing hospital-related deconditioning in frail older adults. However, causality cannot be inferred and further research is needed to investigate causal mechanisms

Surface and Temporal Biosignatures

Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems