Headache in Patients with Sellar Disease: Clinicomorphological Predictors of Headache and the Outcome of Endoscopic Transsphenoidal Surgery.

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.

Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement.

ABSTRACT: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.

Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

Modelling Fatigue Crack Growth in High-Density Polyethylene and Acrylonitrile Butadiene Styrene Polymers.

Prior studies into fatigue crack growth (FCG) in fibre-reinforced polymer composites have shown that the two methodologies of Simple-Scaling and the Hartman-Schijve crack growth equation, which is based on relating the FCG rate to the Schwalbe crack driving force, Δκ, were able to account for differences observed in the measured delamination growth curves. The present paper reveals that these two approaches are also able to account for differences seen in plots of the rate of crack growth, da/dt, versus the range of the imposed stress intensity factor, ΔK, associated with fatigue tests on different grades of high-density polyethylene (HDPE) polymers, before and after electron-beam irradiation, and for tests conducted at different R ratios. Also, these studies are successfully extended to consider FCG in an acrylonitrile butadiene styrene (ABS) polymer that is processed using both conventional injection moulding and additive-manufactured (AM) 3D printing.

Characterisation of Symptom and Polysomnographic Profiles Associated with Cardiovascular Risk in a Sleep Clinic Population with Obstructive Sleep Apnoea.

Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.

A technique for determining the midline using a facebow.

This dental technique described assists the clinician with determining the maxillary midline and for the maxillary midline to coincide with the facial midline. This is accomplished during the acquisition of a facebow registration which is often utilized during prosthetic rehabilitation.

Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases.

C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 "real-world" cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).

Applying Metabolomics and Aptamer-based Proteomics to Determine Pathophysiologic Differences in Decompensated Cirrhosis Patients Hospitalized with Acute Kidney Injury.

Methods A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.

Effect of Spinopelvic Parameters on Outcomes After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

BACKGROUND: Spinopelvic parameters, including pelvic tilt (PT), sacral slope (SS), and pelvic incidence, have been developed to characterize the relationship between lumbar spine and hip motion, but a paucity of literature is available characterizing differences in spinopelvic parameters among patients with femoroacetabular impingement syndrome (FAIS) versus patients without FAIS, as well as the effect of these parameters on outcomes of arthroscopic treatment of FAIS. PURPOSE: To (1) identify differences in spinopelvic parameters between patients with FAIS versus controls without FAIS; (2) identify associations between spinopelvic parameters and preoperative patient-reported outcomes (PROs); and (3) identify differences in PROs between patients with stiff spines (standing-sitting ΔSS ≤10°) versus those without. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The study enrolled patients ≥18 years of age who underwent primary hip arthroscopy for treatment of FAIS with cam, pincer, or mixed (cam and pincer) morphology. Participants underwent preoperative standing-sitting imaging with a low-dose 3-dimensional radiography system and were matched on age and body mass index (BMI) to controls without FAIS who also underwent EOS imaging. Spinopelvic parameters measured on EOS films were compared between the FAIS and control groups. Patients with FAIS completed the modified Harris Hip Score (mHHS) and Non-Arthritic Hip Score (NAHS) before surgery and at 1-year follow-up. Outcome scores were compared between patients with stiff spines versus those without. Associations between spinopelvic parameters and baseline outcome scores were assessed with Pearson correlations. Continuous variables were compared with Student t test and/or Mann-Whitney U test, and categorical variables were compared with Fisher exact test. RESULTS: A total of 50 patients with FAIS (26 men; 24 women; mean age, 36.1 ± 10.7 years; mean BMI, 25.6 ± 4.2) were matched to 30 controls without FAIS (13 men; 17 women; mean age, 36.6 ± 9.5 years; mean BMI, 26.7 ± 3.6). Age, sex, and BMI were not significantly different between the FAIS and control groups (P > .05). Standing PT was not significantly different between stiff and non-stiff cohorts (P = .73), but sitting PT in the FAIS group was more than double that of the control group (36.5° vs 15.0°; P < .001). Incidence of stiff spine was significantly higher in the FAIS group (62.0% vs 3.3%; P < .001). Among FAIS patients, those with stiff spines had a significantly higher prevalence of cam impingement, whereas those with non-stiff spines had a higher prevalence of mixed impingement (P = .04). No significant differences were seen in preoperative mHHS or NAHS scores or pre- to postoperative improvement in scores between FAIS patients with stiff spines versus those without (P > .05), but a greater sitting SS was found to be positively correlated with a higher baseline mHHS (r = 0.36; P = .02). CONCLUSION: Patients with FAIS were more likely to have a stiff spine (standing-sitting ΔSS ≤10°) compared with control participants without FAIS. FAIS patients with stiff spines were more likely to have isolated cam morphology than patient without stiff spines. Although sitting SS was positively correlated with baseline mHHS, no significant differences were seen in 1-year postoperative outcomes between FAIS patients with versus without stiff spine.

Development and stability analysis of carpal kinematic metrics from 4D magnetic resonance imaging.

OBJECTIVE: To develop MRI-derived carpal kinematic metrics and investigating their stability. METHODS: The study used a 4D MRI method to track scaphoid, lunate, and capitate movements in the wrist. A panel of 120 metrics for radial-ulnar deviation and flexion-extension was created using polynomial models of scaphoid and lunate movements relative to the capitate. Intraclass correlation coefficients (ICCs) analyzed intra- and inter-subject stability in 49 subjects, 20 with and 29 without wrist injury history. RESULTS: Comparable degrees of stability were observed across the two different wrist movements. Among the total 120 derived metrics, distinct subsets demonstrated high stability within each type of movement. For asymptomatic subjects, 16 out of 17 metrics with high intra-subject stability also showed high inter-subject stability. The differential analysis of ICC values for each metric between asymptomatic and symptomatic cohorts revealed specific metrics (although relatively unstable) exhibiting greater variability in the symptomatic cohort, thereby highlighting the impact of wrist conditions on the variability of kinematic metrics. CONCLUSION: The findings demonstrate the developing potential of dynamic MRI for assessing and characterizing complex carpal bone dynamics. Stability analyses of the derived kinematic metrics revealed encouraging differences between cohorts with and without wrist injury histories. Although these broad metric stability variations highlight the potential utility of this approach for analyzing carpal instability, further studies are necessary to better characterize these observations.

Bounds to electron spin qubit variability for scalable CMOS architectures.

Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO2 as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO2 interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results. Atomistic tight binding and path integral Monte Carlo methods are adapted to describe fluctuations in devices with millions of atoms by directly analysing their wavefunctions and electron paths instead of their energy spectra. We correlate the effect of roughness with the variability in qubit position, deformation, valley splitting, valley phase, spin-orbit coupling and exchange coupling. These variabilities are found to be bounded, and they lie within the tolerances for scalable architectures for quantum computing as long as robust control methods are incorporated.

Opportunities to improve goat production and food security in Botswana through forage nutrition and the use of supplemental feeds.

Goats fulfil a central role in food and nutritional security across Africa with over half of households owning or rearing goats in rural areas. However, goat performance is poor and mortality high. This study assessed the nutritional quality of commonly used feeds and proposes feed-baskets to enhance goat nutrition and health. Feeds were collected from 11 areas within the Central District of Botswana, and macronutrient analyses were conducted, including crude protein, fibre fractions, ash, and metabolizable energy (ME). Forage nutrition was compared across seasons and soil types. Additionally, seasonal supplementation trials were conducted to evaluate consumption rates of various supplements, including crop residues, pellets, Lablab purpureus, and Dichrostachys cinerea. Each supplement was provided ad libitum for a 24-h period, and consumption rates determined. Findings revealed significant differences in nutrition among various feed sources, across seasons, and in relation to soil types (p < 0.001). Consumption rates of supplements were higher during the dry season, possibly due to reduced forage availability. Supplement consumption rates varied across supplement type, with crop residues accounting for approximately 1% of dry matter intake, compared to up to 45% for pellets, 13% for L. purpureus, and 15% for D. cinerea. While wet season feed baskets exhibited higher ME values compared to dry-season feed-baskets, the relative impact of supplementation was more pronounced during the dry season. These results highlight the potential for optimizing goat diets through improved grazing and browsing management, especially during the reduced nutritional availability in the dry season in Botswana. Such diet optimisation may improve goat health and productivity, which may positively impact the food and financial security of smallholders by providing both increased yields and increased resilience. Importantly, rural communities can experience some of the lowest food security levels in the region. The interventions explored in this study utilise natural capital, often freely available, which can be deployed through existing husbandry systems, potentially making them accessible and practical to smallholders.

Left hemisphere lateralization of the limbic system and frontoparietal network (FPN) correlates with positive and negative symptom improvement following cannabidiol (CBD) administration in psychosis and ultra-high risk (UHR) populations: A voxel-wise meta-analysis.

This voxel-wise meta-analysis assesses current findings about the neural correlates of cannabidiol on the positive and negative symptoms among individuals with psychosis or ultra-high risk (UHR) for psychosis. We used PubMed, EMBASE, and ScienceDirect as primary databases and initially retrieved 157 studies. After applying our eligibility criteria, 13 studies remained for inclusion. Ten studies focused on psychosis. Three studies focused on UHR. Quality assessment was performed for included articles using the RoB2 instrument. Statistical analysis implicated a voxel-wise meta-analysis of different task paradigms (emotion recognition, verbal memory recall, and inhibitory control) with a jackknife sensitivity measure, Egger's test of random effects, and a meta-regression with relevant covariates. Article quality was determined to be primarily low risk of bias, with some elements of unclear bias figuring across studies. Our results showed robust, convergent correlations between CBD administration and left hemisphere lateralization of limbic system and frontoparietal network (FPN) subregions across task paradigms in psychosis and UHR populations. Our meta-regression revealed that decreased limbic system activity correlated with positive symptom improvements, and decreased FPN activity correlated with negative symptom improvements. Lastly, sensitivity analyses determined that there was minimal risk bias or risk of confounding variables unduly influencing our meta-analyses (p > 0.05).

Clinical outcomes of open Latarjet-Patte procedures performed for recurrent anterior shoulder instability with primary bone loss versus failed arthroscopic Bankart repair.

Background: The purpose of this study is to compare the outcomes of Latarjet-Patte procedures (LPs) performed for primary glenohumeral instability surgery in the setting of critical bone loss (LP-BL) versus salvage surgery performed after a failed primary arthroscopic Bankart repair (LP-FB). Methods: Patients who underwent an LP from 2017 to 2021 were identified from the senior author's database and separated into cohorts by LP indication. Data abstracted from electronic medical records included demographic information, preoperative clinical scores, radiological imaging, and complications. Postoperative clinical outcome scores collected after a 2-year minimum follow-up included: patient-reported outcomes measurement information system (PROMIS) upper extremity (UE), PROMIS Pain interference, PROMIS pain intensity, American Shoulder and Elbow Surgeons (ASES), and Visual Analog Scale pain scores. Results: A total of 47 patients (LP-BL: n=29, LP-FB: n=18) with a mean age of 29 years (range, 15-58 years) were included in this study. Both cohorts achieved good upper extremity functionality without significant differences as indicated by mean PROMIS UE (LP-BL: 52.6±10.0 vs. LP-FB: 54.6±7.6, P=0.442) and ASES scores (LP-BL: 89.9±15.7 vs. LP-FB: 91.5±14.4, P=0.712). However, the LP-FB cohort reported lower levels of pain (LP-FB: 0.5±1.1 vs. LP-BL: 1.9±2.7, P=0.020) at their latest follow-up. There were no significant differences in complication rates including re-dislocation between cohorts (LP-BL: 2/29 [6.9%] vs. LP-FB: 2/18 [11.1%], P=0.629). Conclusions: When performed after failed Bankart repair, the LP results in similar postoperative functional outcomes and similar rates of complications and re-dislocations when compared to the primary indication of recurrent glenohumeral instability in the setting of critical bone loss.

Prairie restoration promotes the abundance and diversity of mutualistic arbuscular mycorrhizal fungi.

Predicting how biological communities assemble in restored ecosystems can assist in conservation efforts, but most research has focused on plants, with relatively little attention paid to soil microbial organisms that plants interact with. Arbuscular mycorrhizal (AM) fungi are an ecologically significant functional group of soil microbes that form mutualistic symbioses with plants and could therefore respond positively to plant community restoration. To evaluate the effects of plant community restoration on AM fungi, we compared AM fungal abundance, species richness, and community composition of five annually cultivated, conventionally managed agricultural fields with paired adjacent retired agricultural fields that had undergone prairie restoration 5-9 years prior to sampling. We hypothesized that restoration stimulates AM fungal abundance and species richness, particularly for disturbance-sensitive taxa, and that gains of new taxa would not displace AM fungal species present prior to restoration due to legacy effects. AM fungal abundance was quantified by measuring soil spore density and root colonization. AM fungal species richness and community composition were determined in soils and plant roots using DNA high-throughput sequencing. Soil spore density was 2.3 times higher in restored prairies compared to agricultural fields, but AM fungal root colonization did not differ between land use types. AM fungal species richness was 2.7 and 1.4 times higher in restored prairies versus agricultural fields for soil and roots, respectively. The abundance of Glomeraceae, a disturbance-tolerant family, decreased by 25% from agricultural to restored prairie soils but did not differ in plant roots. The abundance of Claroideoglomeraceae and Diversisporaceae, both disturbance-sensitive families, was 4.6 and 3.2 times higher in restored prairie versus agricultural soils, respectively. Species turnover was higher than expected relative to a null model, indicating that AM fungal species were gained by replacement. Our findings demonstrate that restoration can promote a relatively rapid increase in the abundance and diversity of soil microbial communities that had been degraded by decades of intensive land use, and community compositional change can be predicted by the disturbance tolerance of soil microbial taxonomic and functional groups.

Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.

Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRα and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.

Harm Reduction for Opioid Use Disorder: Strategies and Outcome Metrics.

Tweet: The authors discuss harm reduction strategies and associated outcome metrics in relation to the ongoing opioid crisis.

Krisp: A Python package to aid in the design of CRISPR and amplification-based diagnostic assays from whole genome sequencing data.

Recent pandemics like COVID-19 highlighted the importance of rapidly developing diagnostics to detect evolving pathogens. CRISPR-Cas technology has recently been used to develop diagnostic assays for sequence-specific recognition of DNA or RNA. These assays have similar sensitivity to the gold standard qPCR but can be deployed as easy to use and inexpensive test strips. However, the discovery of diagnostic regions of a genome flanked by conserved regions where primers can be designed requires extensive bioinformatic analyses of genome sequences. We developed the Python package krisp to aid in the discovery of primers and diagnostic sequences that differentiate groups of samples from each other, using either unaligned genome sequences or a variant call format (VCF) file as input. Krisp has been optimized to handle large datasets by using efficient algorithms that run in near linear time, use minimal RAM, and leverage parallel processing when available. The validity of krisp results has been demonstrated in the laboratory with the successful design of a CRISPR diagnostic assay to distinguish the sudden oak death pathogen Phytophthora ramorum from closely related Phytophthora species. Krisp is released open source under a permissive license with all the documentation needed to quickly design CRISPR-Cas diagnostic assays.