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Abstract Background After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin. To emulate this process in canines, a heparin injection and lipid infusion are used, leading to similar fatty acids in the blood. The aim of this study was to examine the effect of glucose suppression on the uptake of FDG in the infarcted myocardial tissue and also on the determination of ECV in both the infarcted tissue and in the myocardium remote to the zone of infarction during a long constant infusion of FDG and Gd-DTPA. Results Extracellular volume was affected neither by suppression nor the length of the constant infusion in remote and infarcted tissue. Metabolic rate of glucose in infarcted tissue decreased during and after suppression of glucose uptake by lipid infusion and heparin injection. An increase in fibrosis and inflammatory cells was found in the center of the infarct as compared to remote tissue. Conclusion The decrease in the metabolic rate of glucose in the infarcted tissue suggests that inflammatory cells may be affected by glucose suppression through heparin injection and lipid infusion.

The streptococcal enzymes IdeS and EndoS cleave IgG antibodies with exquisite substrate specificity, which has enabled their development as clinical and biotechnological tools. Here, the authors present crystal structures of both enzymes in complex with their IgG1 Fc substrate.

It is unclear why hemorrhagic myocardial infarctions (hMI) are destined for adverse outcomes. Here, the authors show that hMI drives fatty degeneration of infarct territories and contributes to adverse remodeling of the heart, which can be mitigated via timely depletion of iron within the hMI zone.

Abstract Background There is increasing recognition that prehabilitation is important as a means of preparing patients physically and psychologically for cancer treatment. However, little is understood about the role and optimal nature of prehabilitation for gynaecological cancer patients, who usually face extensive and life-changing surgery in addition to other treatments that impact significantly on physiological and psychosexual wellbeing. Review question This scoping review was conducted to collate the research evidence on multimodal prehabilitation in gynaecological cancers and the related barriers and facilitators to engagement and delivery that should be considered when designing a prehabilitation intervention for this group of women. Methods Seven medical databases and four grey literature repositories were searched from database inception to September 2021. All articles, reporting on multimodal prehabilitation in gynaecological cancers were included in the final review, whether qualitative, quantitative or mixed-methods. Qualitative studies on unimodal interventions were also included, as these were thought to be more likely to include information about barriers and facilitators which could also be relevant to multimodal interventions. A realist framework of context, mechanism and outcome was used to assist interpretation of findings. Results In total, 24 studies were included in the final review. The studies included the following tumour groups: ovarian only (n = 12), endometrial only (n = 1), mixed ovarian, endometrial, vulvar (n = 5) and non-specific gynaecological tumours (n = 6). There was considerable variation across studies in terms of screening for prehabilitation, delivery of prehabilitation and outcome measures. Key mechanisms and contexts influencing engagement with prehabilitation can be summarised as: (1) The role of healthcare professionals and organisations (2) Patients’ perceptions of acceptability (3) Factors influencing patient motivation (4) Prehabilitation as a priority (5) Access to prehabilitation. Implications for practice A standardised and well evidenced prehabilitation programme for women with gynaecological cancer does not yet exist. Healthcare organisations and researchers should take into account the enablers and barriers to effective engagement by healthcare professionals and by patients, when designing and evaluating prehabilitation for gynaecological cancer patients.

For women achieving clinical remission after the completion of initial treatment for epithelial ovarian cancer, 80% with advanced-stage disease will develop recurrence. However, the standard treatment of women with recurrent platinum-sensitive diseases remains poorly defined. Secondary (SCS), tertiary (TCS) or quaternary (QCS) cytoreduction surgery for recurrence has been suggested to be associated with increased overall survival (OS). We searched five databases for studies reporting death rate, OS, cytoreduction rates, post-operative morbidity/mortality and diagnostic models predicting complete cytoreduction in a platinum-sensitive disease recurrence setting. Death rates calculated from raw data were pooled based on a random-effects model. Meta-regression/linear regression was performed to explore the role of complete or optimal cytoreduction as a moderator. Pooled death rates were 45%, 51%, 66% for SCS, TCS and QCS, respectively. Median OS for optimal cytoreduction ranged from 16–91, 24–99 and 39–135 months for SCS, TCS and QCS, respectively. Every 10% increase in complete cytoreduction rates at SCS corresponds to a 7% increase in median OS. Complete cytoreduction rates ranged from 9–100%, 35–90% and 33–100% for SCS, TCS and QCS, respectively. Major post-operative thirty-day morbidity was reported to range from 0–47%, 13–33% and 15–29% for SCS, TCS and QCS, respectively. Thirty-day post-operative mortality was 0–6%, 0–3% and 0–2% for SCS, TCS and QCS, respectively. There were two externally validated diagnostic models predicting complete cytoreduction at SCS, but none for TCS and QCS. In conclusion, our data confirm that maximal effort higher order cytoreductive surgery resulting in complete cytoreduction can improve survival.

BackgroundLeft-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured.MethodIn five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method.ResultsMBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories.ConclusionIn this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

Abstract Background Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. Materials and methods Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. Results At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p

Background and purpose: Prostate specific membrane antigen positron emission tomography imaging (PSMA-PET) has demonstrated potential for intra-prostatic lesion localization. We leveraged our existing database of co-registered PSMA-PET imaging with cross sectional digitized pathology to model dose coverage of histologically-defined prostate cancer when tailoring brachytherapy dose escalation based on PSMA-PET imaging. Materials and methods: Using a previously-developed automated approach, we created segmentation volumes delineating underlying dominant intraprostatic lesions for ten men with co-registered pathology-imaging datasets. To simulate realistic high-dose-rate brachytherapy (HDR-BT) treatments, we registered the PSMA-PET-defined segmentation volumes and underlying cancer to 3D trans-rectal ultrasound images of HDR-BT cases where 15 Gray (Gy) was delivered. We applied dose/volume optimization to focally target the dominant intraprostatic lesion identified on PSMA-PET. We then compared histopathology dose for all high-grade cancer within whole-gland treatment plans versus PSMA-PET-targeted plans. Histopathology dose was analyzed for all clinically significant cancer with a Gleason score of 7or greater. Results: The standard whole-gland plans achieved a median [interquartile range] D98 of 15.2 [13.8–16.4] Gy to the histologically-defined cancer, while the targeted plans achieved a significantly higher D98 of 16.5 [15.0–19.0] Gy (p = 0.007). Conclusion: This study is the first to use digital histology to confirm the effectiveness of PSMA-PET HDR-BT dose escalation using automatically generated contours. Based on the findings of this study, PSMA-PET lesion dose escalation can lead to increased dose to the ground truth histologically defined cancer.

Background Research from the International Cancer Benchmarking Partnership (ICBP) demonstrates that international variation in lung cancer survival persists, particularly within early stage disease. There is a lack of international consensus on the critical contributing components to variation in lung cancer outcomes and the steps needed to optimise lung cancer services. These are needed to improve the quality of options for and equitable access to treatment, and ultimately improve survival. Methods Semi-structured interviews were conducted with 9 key informants from ICBP countries. An international clinical network representing 6 ICBP countries (Australia, Canada, Denmark, England, Ireland, New Zealand, Northern Ireland, Scotland & Wales) was established to share local clinical insights and examples of best practice. Using a modified Delphi consensus model, network members suggested and rated recommendations to optimise the management of lung cancer. Calls to Action were developed via Delphi voting as the most crucial recommendations, with Good Practice Points included to support their implementation. Results Five Calls to Action and thirteen Good Practice Points applicable to high income, comparable countries were developed and achieved 100% consensus. Calls to Action include (1) Implement cost-effective, clinically efficacious, and equitable lung cancer screening initiatives; (2) Ensure diagnosis of lung cancer within 30 days of referral; (3) Develop Thoracic Centres of Excellence; (4) Undertake an international audit of lung cancer care; and (5) Recognise improvements in lung cancer care and outcomes as a priority in cancer policy. Conclusion The recommendations presented are the voice of an expert international lung cancer clinical network, and signpost key considerations for policymakers in countries within the ICBP but also in other comparable high-income countries. These define a roadmap to help align and focus efforts in improving outcomes and management of lung cancer patients globally.

Abstract Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite these changes, few studies have assessed real‐world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first‐line treatment, while most members (54.6%) received combination therapy as second‐line treatment. All‐cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all‐cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.

BackgroundAtrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established.ObjectiveWe aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation.MethodsTwelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD.ResultsVolumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog.ConclusionPersistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.

Abstract Background The evidence on the impact of patient-prosthesis Mismatch (PPM) on survival thus far has been conflicting. The aim of this study was to 1) study the effect of PPM on survival after isolated aortic and mitral valve replacement and 2) Assess the interaction between left ventricular function and PPM on survival. Methods The study cohort was patients who underwent isolated Aortic valve replacement (AVR) and Mitral valve replacement (MVR) over a 10-year period from 2008 to 2018. PPM was defined using the projected indexed effective orifice area (EOAi). The cohort was divided into different groups based on the degree of PPM. The severity of PPM was classified using threshold values of EOAi used in the literature. The Kaplan- Meier method was used to compare survival by degree of PPM. Multivariate Cox proportional hazards models were used to generate adjusted hazard ratios (HR) with 95% confidence intervals. An interactive term for ejection fraction (EF) was added to test whether EF modifies the effect of the PPM grade on survival. In addition, sub-group analysis based on left ventricular function was performed. Results In the AVR cohort, there were a total of 1953 patients. The distribution of patients in the different PPM categories was as follows: no PPM 59.7%; moderate PPM 36.8%; severe PPM 3.5%. There was no significant difference in survival between the different groups. At 10 years, the adjusted HR between patients with severe PPM versus no PPM was 1.1(CI 0.5–2.4, p > 0.05) and the HR between those with moderate PPM versus no PPM was 0.97 (CI 0.74–1.23, p > 0.05). In the MVR cohort, there were a total of 298 patients. The distribution of PPM is as follows: no PPM 59.4%; and with PPM 40.6%. Again, there was no significant difference in survival between the groups. At 5 years, the adjusted HR between patients with PPM versus no PPM was 1.45 (CI 0.67–3.14, p > 0.05). In both groups, there was no significant interaction between left ventricular function (LVF) and degree of PPM on survival. Conclusions In our study cohort, the degree of PPM was not an independent predictor of survival after AVR or MVR. There was also no significant interaction between LV function and degree of PPM on survival.

Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells.Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves.Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1β, IL-1ra, and VEGF were higher on days 1–2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging.Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.

Abstract Background Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To our knowledge, the only two arrays used today for hybrid PET/MRI cardiovascular imaging are either incapable of achieving high acceleration or affect the PET photon count greatly. Purpose This study is focused on the evaluation of the MRI performance of a novel third-party prototype 32-channel phased array designed for simultaneous PET/MRI cardiovascular imaging. The study compares the quality parameters of MRI parallel imaging, such as g-factor, noise correlation coefficients, and SNR, to the conventional arrays (mMR 12-channel and MRI-only 32-channel) currently used with hybrid PET/MRI systems. The quality parameters of parallel imaging were estimated for multiple acceleration factors on a phantom and three healthy volunteers. Using a Germanium-68 (Ge-68) phantom, preliminary measurements of PET photon attenuation caused by the novel array were briefly compared to the photon counts produced from no-array measurements. Results The global mean of the g-factor and SNRg produced by the novel 32-channel PET/MRI array were better than those produced by the MRI-only 32-channel array by 5% or more. The novel array has resulted in MRI SNR improvements of > 30% at all acceleration factors, in comparison to the mMR12-channel array. Preliminary evaluation of PET transparency showed less than 5% photon attenuation caused by both anterior and posterior parts of the novel array. Conclusions The MRI performance of the novel PET/MRI 32-channel array qualifies it to be a viable alternative to the conventional arrays for cardiovascular hybrid PET/MRI. A detailed evaluation of the novel array’s PET performance remains to be conducted, but cursory assessment promises significantly reduced attenuation.

Abstract Background Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. Methods This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. Discussion When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. Trial registration International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

Ovarian sarcomas account for 1% of all ovarian malignancies and amongst these, primary ovarian leiomyosarcoma is the rarest subtype. Primary ovarian leiomyosarcoma has a very poor prognosis, with less than 20% of patients being alive at 5 years. Only a few cases have been published in the literature and there is very limited knowledge on the clinical behaviour and optimal management of these tumours. We have performed a retrospective analysis of a prospectively maintained database to identify all primary ovarian leiomyosarcoma diagnosed and treated at the Royal Marsden NHS Foundation Trust between 1998 and 2020. Sixteen patients were identified from our database and fifteen were eligible for the analysis. Twelve patients presented with localized disease and underwent initial surgery and three patients had metastatic disease at presentation. Recurrence-free survival post-surgery was 16 months. Eight patients received first-line chemotherapy and four patients received second-line chemotherapy. Two patients had indolent metastatic disease and benefited from local therapies only. The median overall survival in the metastatic setting in our cohort was 51 months, which is consistent with previously published cases. Primary ovarian leiomyosarcoma is an extremely rare malignancy with a poor prognosis. This study is the largest case series of primary ovarian leiomyosarcoma published to date, providing clinically important information regarding survival and metastatic rate as well as treatment outcomes in the metastatic setting.

Purpose: Since collecting outcome measure data from patients can be expensive, time-consuming, and subject to memory and nonresponse bias, we sought to learn whether outcomes important to patients can be obtained from data in the electronic health record (EHR) or health insurance claims. Methods: We previously identified 21 outcomes rated important by patients who had advanced imaging tests for back or abdominal pain. Telephone surveys about experiencing those outcomes 1 year after their test from 321 people consenting to use of their medical record and claims data were compared with audits of the participants’ EHR progress notes over the time period between the imaging test and survey completion. We also compared survey data with algorithmically extracted data from claims files for outcomes for which data might be available from that source. Results: Of the 16 outcomes for which patients’ survey responses were considered to be the best information source, only 2 outcomes for back pain and 3 for abdominal pain had kappa scores above a very modest level of ≥ 0.2 for chart audit of EHR data and none for algorithmically obtained EHR/claims data. Of the other 5 outcomes for which claims data were considered to be the best information source, only 2 outcomes from patient surveys and 3 outcomes from chart audits had kappa scores ≥ 0.2. Conclusions: For the types of outcomes studied here, medical record or claims data do not provide an adequate source of information except for a few outcomes where patient reports may be less accurate.

Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology.

When forensic scientists evaluate and report on the probative strength of single DNA traces, they commonly rely on only one number, expressing the rarity of the DNA profile in the population of interest. This is so because the focus is on propositions regarding the source of the recovered trace material, such as ‘the person of interest is the source of the crime stain’. In particular, when the alternative proposition is ‘an unknown person is the source of the crime stain’, one is directed to think about the rarity of the profile. However, in the era of DNA profiling technology capable of producing results from small quantities of trace material (i.e., non-visible staining) that is subject to easy and ubiquitous modes of transfer, the issue of source is becoming less central, to the point that it is often not contested. There is now a shift from the question ‘whose DNA is this?’ to the question ‘how did it get there?’. As a consequence, recipients of expert information are now very much in need of assistance with the evaluation of the meaning and probative strength of DNA profiling results when the competing propositions of interest refer to different activities. This need is widely demonstrated in day-to-day forensic practice and is also voiced in specialized literature. Yet many forensic scientists remain reluctant to assess their results given propositions that relate to different activities. Some scientists consider evaluations beyond the issue of source as being overly speculative, because of the lack of relevant data and knowledge regarding phenomena and mechanisms of transfer, persistence and background of DNA. Similarly, encouragements to deal with these activity issues, expressed in a recently released European guideline on evaluative reporting 42, which highlights the need for rethinking current practice, are sometimes viewed skeptically or are not considered feasible. In this discussion paper, we select and discuss recurrent skeptical views brought to our attention, as well as some of the alternative solutions that have been suggested.

This study employed an independent-groups design (4 conditions) to investigate possible biases in the suicide risk perception of mental health professionals. Four hundred participants comprising doctors, nurses and social workers viewed a vignette describing a fictitious patient with a long-term mental illness. The case was presented as being drawn from a sample of twenty similar clinical case reports, of which 10 were associated with an outcome of suicide. The participant tasks were (i) to decide whether the presented vignette was one of those cases or not, and (ii) to provide an assessment of confidence in that decision. The 4 conditions were used to investigate whether the presence of an associated face, and the nature of the emotional state expressed by that face, affected the response profile. In fact, there were no significant differences between conditions, but there was a significant bias across all conditions towards associating the vignette with suicide, despite the base rate being pre-determined at 50%. The bias was more pronounced in doctors and in male respondents. Moreover, many participants indicated substantial confidence in their decisions. The results are discussed in terms of availability bias and over-confidence bias.

Frequency-domain photon migration (FDPM) is a noninvasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, μa, and scattering, μs′, parameters) derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin (total, oxy-, and deoxyforms), oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and in situ) and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.

A short, high-yielding synthesis of the antitumour agent irisquinone (1) is described. The key steps are the palladium catalysed coupling reaction of dec-9-yn-1-ol with iodide (2) to form alkyne (3) and the Fremy’s salt oxidation of phenol (7).

This letter presents an experimental study that shows that a 3(rd) physical dimension may be used to further increase information packing density in magnetic storage devices. We demonstrate the feasibility of at least quadrupling the magnetic states of magnetic-based data storage devices by recording and reading information from nanopillars with three magnetically-decoupled layers. Magneto-optical Kerr effect microscopy and magnetic force microscopy analysis show that both continuous (thin film) and patterned triple-stack magnetic media can generate eight magnetically-stable states. This is in comparison to only two states in conventional magnetic recording. Our work further reveals that ferromagnetic interaction between magnetic layers can be reduced by combining Co/Pt and Co/Pd multilayers media. Finally, we are showing for the first time an MFM image of multilevel-3D bit patterned media with 8 discrete signal levels.