Nightly sleep duration predicts grade point average in the first year of college.

Academic achievement in the first year of college is critical for setting students on a pathway toward long-term academic and life success, yet little is known about the factors that shape early college academic achievement. Given the important role sleep plays in learning and memory, here we extend this work to evaluate whether nightly sleep duration predicts change in end-of-semester grade point average (GPA). First-year college students from three independent universities provided sleep actigraphy for a month early in their winter/spring academic term across five studies. Findings showed that greater early-term total nightly sleep duration predicted higher end-of-term GPA, an effect that persisted even after controlling for previous-term GPA and daytime sleep. Specifically, every additional hour of average nightly sleep duration early in the semester was associated with an 0.07 increase in end-of-term GPA. Sensitivity analyses using sleep thresholds also indicated that sleeping less than 6 h each night was a period where sleep shifted from helpful to harmful for end-of-term GPA, relative to previous-term GPA. Notably, predictive relationships with GPA were specific to total nightly sleep duration, and not other markers of sleep, such as the midpoint of a student's nightly sleep window or bedtime timing variability. These findings across five studies establish nightly sleep duration as an important factor in academic success and highlight the potential value of testing early academic term total sleep time interventions during the formative first year of college.

Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.

Glioblastoma is characterized by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganization of neural connectivity. Quantifying neural connectivity in glioblastoma may provide a valuable tool for identifying tumour invasion. Here we propose an approach to systematically identify tumour invasion by quantifying the structural connectome in glioblastoma patients. We first recruit two independent prospective glioblastoma cohorts: the discovery cohort with 117 patients and validation cohort with 42 patients. Next, we use diffusion MRI of healthy subjects to construct tractography templates indicating white matter connection pathways between brain regions. Next, we construct fractional anisotropy skeletons from diffusion MRI using an improved voxel projection approach based on the tract-based spatial statistics, where the strengths of white matter connection and brain regions are estimated. To quantify the disrupted connectome, we calculate the deviation of the connectome strengths of patients from that of the age-matched healthy controls. We then categorize the disruption into regional disruptions on the basis of the relative location of connectome to focal lesions. We also characterize the topological properties of the patient connectome based on the graph theory. Finally, we investigate the clinical, cognitive and prognostic significance of connectome metrics using Pearson correlation test, mediation test and survival models. Our results show that the connectome disruptions in glioblastoma patients are widespread in the normal-appearing brain beyond focal lesions, associated with lower preoperative performance (P < 0.001), impaired cognitive function (P < 0.001) and worse survival (overall survival: hazard ratio = 1.46, P = 0.049; progression-free survival: hazard ratio = 1.49, P = 0.019). Additionally, these distant disruptions mediate the effect on topological alterations of the connectome (mediation effect: clustering coefficient -0.017, P < 0.001, characteristic path length 0.17, P = 0.008). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of connectivity reorganization, where the increased neural connectivity is associated with better overall survival (log-rank P = 0.005). In conclusion, our connectome approach could reveal and quantify the glioblastoma invasion distant from the focal lesion and invisible on the conventional MRI. The structural disruptions in the normal-appearing brain were associated with the topological alteration of the brain and could indicate treatment target. Our approach promises to aid more accurate patient stratification and more precise treatment planning.

TMQuery: a database of precomputed template modeling scores for assessment of protein structural similarity.

SUMMARY: Comparisons of protein structures are critical for developing novel protein designs, annotating protein functions and predicting protein structure. The template modeling score (TM-score) is a widely used but computationally expensive measure of protein similarity that is applicable to a wide variety of structural biology problems. We introduce TMQuery-a continuously updated database containing over eight billion pre-computed TM-score values for every pair of proteins in the Protein Data Bank, allowing researchers to quickly query and download TM-scores via a web interface. AVAILABILITY AND IMPLEMENTATION: Publicly available at https://tmquery.gsk.com/.

Lack of Belonging Predicts Depressive Symptomatology in College Students.

Feeling a sense of belonging is a central human motivation that has consequences for mental health and well-being, yet surprisingly little research has examined how belonging shapes mental health among young adults. In three data sets from two universities (exploratory study: N = 157; Confirmatory Study 1: N = 121; Confirmatory Study 2: n = 188 in winter term, n = 172 in spring term), we found that lower levels of daily-assessed feelings of belonging early and across the academic term predicted higher depressive symptoms at the end of the term. Furthermore, these relationships held when models controlled for baseline depressive symptoms, sense of social fit, and other social factors (loneliness and frequency of social interactions). These results highlight the relationship between feelings of belonging and depressive symptoms over and above other social factors. This work underscores the importance of daily-assessed feelings of belonging in predicting subsequent depressive symptoms and has implications for early detection and mental health interventions among young adults.

Bimolecular reactions of CH2CN2+ with Ar, N2 and CO: reactivity and dynamics.

The reactivity, energetics and dynamics of bimolecular reactions between CH2CN2+ and three neutral species (Ar, N2 and CO) have been studied using a position sensitive coincidence methodology at centre-of-mass collision energies of 4.3-5.0 eV. This is the first study of bimolecular reactions involving CH2CN2+, a species relevant to the ionospheres of planets and satellites, including Titan. All of the collision systems investigated display two collision-induced dissociation (CID) channels, resulting in the formation of C+ + CH2N+ and H+ + HC2N+. Evidence for channels involving further dissociation of the CID product HC2N+, forming H + CCN+, were detected in the N2 and CO systems. Proton-transfer from the dication to the neutral species occurs in all three of the systems via a direct mechanism. Additionally, there are product channels resulting from single electron transfer following collisions of CH2CN2+ with both N2 and CO, but interestingly no electron transfer following collisions with Ar. Electronic structure calculations of the lowest energy electronic states of CH2CN2+ reveal six local geometric minima: both doublet and quartet spin states for cyclic, linear (CH2CN), and linear isocyanide (CH2NC) molecular geometries. The lowest energy electronic state was determined to be the doublet state of the cyclic dication. The ready generation of C+ ions by collision-induced dissociation suggests that the cyclic or linear isocyanide dication geometries are present in the [CH2CN]2+ beam.

Bimolecular reactions of S2+ with Ar, H2 and N2: reactivity and dynamics.

The reactivity, energetics and dynamics of bimolecular reactions between S2+ and three neutral species (Ar, H2 and N2) have been studied using a position-sensitive coincidence methodology at centre-of-mass collision energies below 6 eV. This is the first study of bimolecular reactions involving S2+, a species detected in planetary ionospheres, the interstellar medium, and in anthropogenic manufacturing processes. The reactant dication beam employed consists predominantly of S2+ in the ground 3P state, but some excited states are also present. Most of the observed reactions involve the ground state of S2+, but the dissociative electron transfer reactions appear to exclusively involve excited states of this atomic dication. We observe exclusively single electron-transfer between S2+ and Ar, a process which exhibits strong forward scatting typical of the Landau-Zener style dynamics observed for other dicationic electron transfer reactions. Following collisions between S2+ + H2, non-dissociative and dissociative single electron-transfer reactions were detected. The dynamics here show evidence for the formation of a long-lived collision complex, [SH2]2+, in the dissociative single electron-transfer channel. The formation of SH+ was not observed. In contrast, the collisions of S2+ + N2 result in the formation of SN+ + N+ in addition to the products of single electron-transfer reactions.

Assessment of neuropsychological function in brain tumor treatment: a comparison of traditional neuropsychological assessment with app-based cognitive screening.

BACKGROUND: Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment. METHODS: Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores. RESULTS: Approximately 2-3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent. CONCLUSIONS: Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed.

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients?

BACKGROUND: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery. METHODS: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression. RESULTS: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months. CONCLUSIONS: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

Host contribution to parasite persistence is consistent between parasites and over time, but varies spatially.

Most parasites and pathogens infect multiple hosts, but a great deal of variation exists in the role of those hosts in persistence of infection. Understanding which hosts are most important in maintaining parasites can provide a clearer target for infection control. Recently developed empirical and theoretical approaches provide a way to quantify the relative contribution of hosts within a community and place them in a multi-host framework to better direct control efforts. Amphibians provide a framework for better understanding multi-host-multi-parasite dynamics. Two well-studied amphibian parasites, Batrachochytrium dendrobatidis (Bd) and Ranavirus, infect multiple host species and exhibit a great deal of heterogeneity in how they affect hosts. We used these two parasites and a community of five amphibian species to investigate the relative importance of hosts in parasite persistence, and how any patterns varied spatially and temporally. At two sites (Lake Ercina and Lake Lloroza in the Picos de Europa National Park, Spain) we collected data on the prevalence and shedding rate of parasite infection for both Bd and Ranavirus, and the abundance of each species' life stages. We used these data to parameterize a recently developed modeling framework, which was used to quantify the relative contribution of each host to the community reproductive number, R0 . By comparing each host-category over time and between sites we were able to identify consistencies in which host was responsible for the maintenance of these two parasites. Within a site one species consistently contributed the most to the persistence of both parasites. This consistency did not transfer between sites, the maintenance host species being different for each. At one site (Ercina), life stages of the common midwife toad, Alytes obstetricans, acted as the maintenance host for both Bd and Ranavirus. In contrast, at the second site, Lloroza, the alpine newt, Ichthyosaura alpestris, fulfilled that role. A single host species was responsible for infection persistence of both parasites at each lake. Attempts to control the infection levels and impacts of multiple parasites can benefit from a community epidemiology approach, and provide clarity on which hosts are the foci of mitigation efforts. However, at a small spatial scale, the target host may vary according to the physical qualities of those sites and the demographics of the host community.

Bond-forming and electron-transfer reactivity between Ar2+ and N2.

Collisions between Ar2+ and N2 have been studied using a coincidence technique at a centre-of-mass (CM) collision energy of 5.1 eV. Four reaction channels generating pairs of monocations are observed: Ar+ + N2+, Ar+ + N+, ArN+ + N+ and N+ + N+. The formation of Ar+ + N2+ is the most intense channel, displaying forward scattering but with a marked tail to higher scattering angles. This scattering, and other dynamics data, is indicative of direct electron transfer competing with a 'sticky' collision between the Ar2+ and N2 reactants. Here Ar+ is generated in its ground (2P) state and N2+ is primarily in the low vibrational levels of the C2Σu+ state. A minor channel involving the initial population of higher energy N2+ states, lying above the dissociation asymptote to N+ + N, which fluoresce to stable states of N2+ is also identified. The formation of Ar+ + N+ by dissociative single electron transfer again reveals the involvement of two different pathways for the initial electron transfer (direct or complexation). This reaction pathway predominantly involves excited states of Ar2+ (1D and 1S) populating N2+* in its dissociative C2Σu+, 22Πg and D2Πg states. Formation of ArN+ + N+ proceeds via a direct mechanism. The ArN+ is formed, with significant vibrational excitation, in its ground (X3Σ-) state. Formation of N+ + N+ is also observed as a consequence of double electron transfer forming N22+. The exoergicity of the subsequent N22+ dissociation reveals the population of the A1Πu and D3Πg dication states.

Ionisation of PF3: absolute partial electron ionisation cross sections and the formation and reactivity of dication states.

Absolute partial electron ionisation cross sections, and precursor-specific partial electron ionisation cross sections, for the formation of cations from phosphorus trifluoride (PF3) are reported over the electron energy range 50-200 eV. The absolute values are determined by the measurement of cross sections relative to the formation of PF3+ using 2D ion-ion coincidence time-of-flight mass spectrometry and subsequent scaling using binary encounter-Bethe calculations of the total ionisation cross section. This new dataset significantly augments the partial ionisation cross sections for electron ionization of PF3 found in literature, addressing previous discrepancies in the branching ratios of product ions, and provides the first values for the precursor-specific cross sections. Comparisons to calculated cross sections from the literature are encouraging, although there are discrepancies for individual ions. The coincidence experiments indicate that double and triple ionisation generate approximately 20% of the cationic ionisation products at 200 eV electron energy. One dissociative dication state, dissociating to PF2+ + F+, is clearly identified as the lowest triplet state of PF32+ and five different dications (PF32+, PF22+, PF2+, P2+ and F2+) are detected in the mass spectra. The dication energetics revealed by the experiments are supported by a computational investigation of the dication's electronic structure. The cross sections reported will allow more accurate modelling of the role of the ionization of PF3 in energetic environments. A first investigation of the bimolecular reactivity of metastable states of PF32+ is also reported. In collisions with Ar, O2 and CO dissociative single electron transfer dominates the product ion yield, whereas collision-induced dissociation of the dication is important following collisions with Ne. Consideration of the energetics of these processes indicates that the reactant dication beam contains ions in both the ground singlet state and the first excited triplet state. The deduction regarding the longevity of the triplet state is supported by metastable signals in the coincidence spectra. Weak signals corresponding to the formation of ArF+ are detected following PF32+ collisions with Ar, and experimental and computational considerations indicate this new chemical bond is formed via a collision complex.

Intraoperative mapping of executive function using electrocorticography for patients with low-grade gliomas.

BACKGROUND: Intraoperative functional mapping with direct electrical stimulation during awake surgery for patients with diffuse low-grade glioma has been used in recent years to optimize the balance between surgical resection and quality of life following surgery. Mapping of executive functions is particularly challenging because of their complex nature, with only a handful of reports published so far. Here, we propose the recording of neural activity directly from the surface of the brain using electrocorticography to map executive functions and demonstrate its feasibility and potential utility. METHODS: To track a neural signature of executive function, we recorded neural activity using electrocorticography during awake surgery from the frontal cortex of three patients judged to have an appearance of diffuse low-grade glioma. Based on existing functional magnetic resonance imaging (fMRI) evidence from healthy participants for the recruitment of areas associated with executive function with increased task demands, we employed a task difficulty manipulation in two counting tasks performed intraoperatively. Following surgery, the data were extracted and analyzed offline to identify increases in broadband high-gamma power with increased task difficulty, equivalent to fMRI findings, as a signature of activity related to executive function. RESULTS: All three patients performed the tasks well. Data were recorded from five electrode strips, resulting in data from 15 channels overall. Eleven out of the 15 channels (73.3%) showed significant increases in high-gamma power with increased task difficulty, 26.6% of the channels (4/15) showed no change in power, and none of the channels showed power decrease. High-gamma power increases with increased task difficulty were more likely in areas that are within the canonical frontoparietal network template. CONCLUSIONS: These results are the first step toward developing electrocorticography as a tool for mapping of executive function complementarily to direct electrical stimulation to guide resection. Further studies are required to establish this approach for clinical use.

The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions.

A core structural and functional motif of the vertebrate central nervous system is discrete clusters of neurons or 'nuclei'. Yet the developmental mechanisms underlying this fundamental mode of organisation are largely unknown. We have previously shown that the assembly of motor neurons into nuclei depends on cadherin-mediated adhesion. Here, we demonstrate that the emergence of mature topography among motor nuclei involves a novel interplay between spontaneous activity, cadherin expression and gap junction communication. We report that nuclei display spontaneous calcium transients, and that changes in the activity patterns coincide with the course of nucleogenesis. We also find that these activity patterns are disrupted by manipulating cadherin or gap junction expression. Furthermore, inhibition of activity disrupts nucleogenesis, suggesting that activity feeds back to maintain integrity among motor neurons within a nucleus. Our study suggests that a network of interactions between cadherins, gap junctions and spontaneous activity governs neuron assembly, presaging circuit formation.

Bond-forming and electron-transfer reactivity between Ar2+ and O2.

The reactivity, energetics and dynamics of the bimolecular reactions between Ar2+ and O2 have been studied using a position sensitive coincidence methodology at a collision energy of 4.4 eV. Four bimolecular reaction channels generating pairs of product ions are observed, forming: Ar+ + O2+, Ar+ + O+, ArO+ + O+ and O+ + O+. The formation of Ar+ + O2+ is a minor channel, involving forward scattering, and generates O2+ in its ground electronic state. This single electron transfer process is expected to be facile by Landau-Zener arguments, but the intensity of this channel is low because the electron transfer pathways involve multi-electron processes. The formation of Ar+ + O+ + O, is the most intense channel following interactions of Ar2+ with O2, in agreement with previous experiments. Many different combinations of Ar2+ and product electronic states contribute to the product flux in this channel. Major dissociation pathways of the nascent O2+* ion involve the ion's first and second dissociation limits. Unusually, the experimental results clearly show the involvement of a short-lived collision complex [ArO2]2+ in this channel. The formation of O+ and ArO+ involves direct abstraction of O- from O2 by Ar2+. There is scant evidence of the involvement of a collision complex in this bond forming pathway. The ArO+ product appears to be formed in the first excited electronic state (2Π). The formation of O+ + O+ results from dissociative double electron transfer via an O22+ intermediate. The exoergicity of the dissociation of the nascent O22+ intermediate is in good agreement with previous work investigating the unimolecular dissociation of this dication.

Choice of molecular assay determines ranavirus detection probability and inferences about prevalence and occurrence.

Ranaviruses are emerging pathogens that can cause morbidity, mortality and population declines in ectothermic hosts; however, there is no standardized approach to diagnostics. Here, we compared the inter-assay variation and intra-assay precision among 2 commonly used quantitative PCRs (qPCRs), a conventional and a nested PCR assay (used as a gold standard), using laboratory-propagated ranavirus (FV3 and CMTV) and field-collected samples. A qPCR assay ('Leung') detected viral DNA in dilutions 2 orders of magnitude lower than other assays regardless of the viral lineage of the cultured isolate (FV3/CMTV). The second qPCR ('Brunner') was slightly more sensitive than the conventional PCR ('Mao' assay). For field samples, the Leung qPCR detected all known positives, while the Mao assay PCR only detected 2.5% of the positive samples. Amplicon sequences from the 2 conventional PCRs were shown to be useful for inferring viral lineage. Inaccurate results will bias estimates of the distribution and prevalence of ranaviruses, and together these findings emphasize that molecular assays should be chosen carefully in the context of study aims.

Deep learning for glioblastoma segmentation using preoperative magnetic resonance imaging identifies volumetric features associated with survival.

BACKGROUND: Measurement of volumetric features is challenging in glioblastoma. We investigate whether volumetric features derived from preoperative MRI using a convolutional neural network-assisted segmentation is correlated with survival. METHODS: Preoperative MRI of 120 patients were scored using Visually Accessible Rembrandt Images (VASARI) features. We trained and tested a multilayer, multi-scale convolutional neural network on multimodal brain tumour segmentation challenge (BRATS) data, prior to testing on our dataset. The automated labels were manually edited to generate ground truth segmentations. Network performance for our data and BRATS data was compared. Multivariable Cox regression analysis corrected for multiple testing using the false discovery rate was performed to correlate clinical and imaging variables with overall survival. RESULTS: Median Dice coefficients in our sample were (1) whole tumour 0.94 (IQR, 0.82-0.98) compared to 0.91 (IQR, 0.83-0.94 p = 0.012), (2) FLAIR region 0.84 (IQR, 0.63-0.95) compared to 0.81 (IQR, 0.69-0.8 p = 0.170), (3) contrast-enhancing region 0.91 (IQR, 0.74-0.98) compared to 0.83 (IQR, 0.78-0.89 p = 0.003) and (4) necrosis region were 0.82 (IQR, 0.47-0.97) compared to 0.67 (IQR, 0.42-0.81 p = 0.005). Contrast-enhancing region/tumour core ratio (HR 4.73 [95% CI, 1.67-13.40], corrected p = 0.017) and necrotic core/tumour core ratio (HR 8.13 [95% CI, 2.06-32.12], corrected p = 0.011) were independently associated with overall survival. CONCLUSION: Semi-automated segmentation of glioblastoma using a convolutional neural network trained on independent data is robust when applied to routine clinical data. The segmented volumes have prognostic significance.

Improvement of the Efficiency and Completeness of Neuro-Oncology Patient Referrals to a Tertiary Center Through the Implementation of an Electronic Referral System: Retrospective Cohort Study.

BACKGROUND: Quality referrals to specialist care are key for prompt, optimal decisions about the management of patients with brain tumors. OBJECTIVE: This study aimed to determine the impact of introducing a Web-based, electronic referral (eReferral) system to a specialized neuro-oncology center, using a service-developed proforma, in terms of waiting times and information completeness. METHODS: We carried out a retrospective cohort study based on the review of medical records of referred adult patients, excluding follow-ups. Primary outcome measures were durations of three key phases within the referral pathway and completion rates of six referral fields. RESULTS: A total of 248 patients were referred to the specialist center during the study period. Median (IQR) diagnostic imaging to referral intervals were 3 (1-5) days with eReferrals, and 9 (4-19), 19 (14-49), and 8 (4-23) days with paper proforma, paper letter, and internal referrals, respectively (P<.001). Median (IQR) referral to multidisciplinary team decision intervals were 3 (2-7), 2 (1-3), 8 (2-24), and 3 (2-6) days respectively (P=.01). For patients having surgery, median (IQR) diagnostic imaging to surgery intervals were 28 (21-41), 34 (27-51), 104 (69-143), and 32 (15-89) days, respectively (P<.001). Proportions of complete fields differed significantly by referral type in all study fields (all with Ps <.001) except for details of presentation, which were present in all referrals. All study fields were always present in eReferrals, as these are compulsory for referral submission. Depending on the data field, level of completeness in the remaining referral types ranged within 69% (65/94) to 87% (82/94), 15% (3/20) to 65% (13/20), and 22% (8/41) to 63% (26/41) in paper proforma, paper letter, and internal referrals, respectively. CONCLUSIONS: An electronic, Web-based, service-developed specific proforma for neuro-oncology referrals performs significantly better, with shorter waiting times and greater completeness of information than other referral types. A wider application of eReferrals is an important first step to streamlining specialist care pathways and providing excellent care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10.2196/15002.

Effects of historic and projected climate change on the range and impacts of an emerging wildlife disease.

The global trend of increasing environmental temperatures is often predicted to result in more severe disease epidemics. However, unambiguous evidence that temperature is a driver of epidemics is largely lacking, because it is demanding to demonstrate its role among the complex interactions between hosts, pathogens, and their shared environment. Here, we apply a three-pronged approach to understand the effects of temperature on ranavirus epidemics in UK common frogs, combining in vitro, in vivo, and field studies. Each approach suggests that higher temperatures drive increasing severity of epidemics. In wild populations, ranavirosis incidents were more frequent and more severe at higher temperatures, and their frequency increased through a period of historic warming in the 1990s. Laboratory experiments using cell culture and whole animal models showed that higher temperature increased ranavirus propagation, disease incidence, and mortality rate. These results, combined with climate projections, predict severe ranavirosis outbreaks will occur over wider areas and an extended season, possibly affecting larval recruitment. Since ranaviruses affect a variety of ectothermic hosts (amphibians, reptiles, and fish), wider ecological damage could occur. Our three complementary lines of evidence present a clear case for direct environmental modulation of these epidemics and suggest management options to protect species from disease.

Multi-parametric and multi-regional histogram analysis of MRI: modality integration reveals imaging phenotypes of glioblastoma.

OBJECTIVES: Integrating multiple imaging modalities is crucial for MRI data interpretation. The purpose of this study is to determine whether a previously proposed multi-view approach can effectively integrate the histogram features from multi-parametric MRI and whether the selected features can offer incremental prognostic values over clinical variables. METHODS: Eighty newly-diagnosed glioblastoma patients underwent surgery and chemoradiotherapy. Histogram features of diffusion and perfusion imaging were extracted from contrast-enhancing (CE) and non-enhancing (NE) regions independently. An unsupervised patient clustering was performed by the multi-view approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of patient clustering to survival. The metabolic signatures of patient clusters were compared using multi-voxel spectroscopy analysis. The prognostic values of histogram features were evaluated by survival and ROC curve analyses. RESULTS: Two patient clusters were generated, consisting of 53 and 27 patients respectively. Cluster 2 demonstrated better overall survival (OS) (p = 0.007) and progression-free survival (PFS) (p < 0.001) than Cluster 1. Cluster 2 displayed lower N-acetylaspartate/creatine ratio in NE region (p = 0.040). A higher mean value of anisotropic diffusion in NE region was associated with worse OS (hazard ratio [HR] = 1.40, p = 0.020) and PFS (HR = 1.36, p = 0.031). The seven features selected by this approach showed significantly incremental value in predicting 12-month OS (p = 0.020) and PFS (p = 0.022). CONCLUSIONS: The multi-view clustering method can provide an effective integration of multi-parametric MRI. The histogram features selected may be used as potential prognostic markers. KEY POINTS: • Multi-parametric magnetic resonance imaging captures multi-faceted tumor physiology. • Contrast-enhancing and non-enhancing tumor regions represent different tumor components with distinct clinical relevance. • Multi-view data analysis offers a method which can effectively select and integrate multi-parametric and multi-regional imaging features.

Non-invasive assessment of glioma microstructure using VERDICT MRI: correlation with histology.

PURPOSE: This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region. METHODS: Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size. RESULTS: VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10-3 mm2/s vs. 0.98 ± 0.38 × 10-3 mm2/s, respectively; p = 0.18). CONCLUSION: This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future. KEY POINTS: • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale.