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Introduction Intervertebral disc (IVD) degeneration is often associated with low back pain and radiating leg pain. The purpose of this study is to develop a reproducible and standardized preclinical model of painful lumbar IVD degeneration by evaluation of structural and behavioral changes in response to IVD injury with increasing needle sizes. This model can be used to develop new therapies for IVD degeneration. Methods Forty‐five female Sprague Dawley rats underwent anterior lumbar disc needle puncture at levels L4‐5 and L5‐6 under fluoroscopic guidance. Animals were randomly assigned to four different experimental groups: needle sizes of 18 Gauge (G), 21G, 23G, and sham control. To monitor the progression of IVD degeneration and pain, the following methods were employed: μMRI, qRT‐PCR, histology, and biobehavioral analysis. Results T1‐ and T2‐weighted μMRI analysis showed a correlation between the degree of IVD degeneration and needle diameter, with the most severe degeneration in the 18G group. mRNA expression of markers for IVD degeneration markers were dysregulated in the 18G and 21G groups, while pro‐nociceptive markers were increased in the 18G group only. Hematoxylin and Eosin (H&E) and Alcian Blue/Picrosirius Red staining confirmed the most pronounced IVD degeneration in the 18G group. Randall‐Selitto and von Frey tests showed increased hindpaw sensitivity in the 18G group. Conclusion Our findings demonstrate that anterior disc injury with an 18G needle creates severe IVD degeneration and mechanical hypersensitivity, while the 21G needle results in moderate degeneration with no increased pain sensitivity. Therefore, needle sizes should be selected depending on the desired phenotype for the pre‐clinical model. Study Design Overview This study establishes and validates a rat model for lumbar IVD degeneration that is reflected in painful behavior. Based on our findings we conclude that annular disc injury with a 18G needle creates severe, painful IVD degeneration, while 21G needle injury results in moderate degeneration.

Purpose Neutral zone (NZ) parameters in spinal biomechanics studies are sensitive to spinal instability, disc degeneration, and repair. Multiple methods in the literature quantify NZ, yet no consensus exists on applicability and comparability of methods. This study compares five different NZ quantification methods using two different load‐deflection profiles. Methods Rat caudal and lumbar motion segments were tested in axial rotation to generate load‐deflection curves with profiles exhibiting prominent distinction between elastic and NZ regions (ie, triphasic) and profiles that did not (ie, viscoelastic). NZ was quantified using five methods: trilinear, double sigmoid (DS), zero load, stiffness threshold (ST), and extrapolated elastic zone. Absolute agreement and consistency of NZ parameters were assessed using intraclass correlation (ICC), Bland‐Altman analyses, and analysis of variance. Results For triphasic profiles, NZ magnitude exhibited high consistency (methods correlate but differ in absolute values), and only some methods exhibited agreement. For viscoelastic profiles, NZ magnitude showed limited consistency and no absolute agreement. NZ stiffness had high agreement and consistency across most methods and profiles. For triphasic profiles, the linear NZ regions for all methods were not well‐described by a linear fit yet for viscoelastic profiles all methods characterized a linear NZ region. Conclusion This NZ comparison study showed surprisingly limited agreement and consistency among NZ parameters with approximately 5% to 100% difference depending on the method and load‐deflection profile. Nevertheless, the DS and ST methods appeared to be most comparable. We conclude that most NZ quantification methods cannot be applied interchangeably, highlighting a need to clearly state NZ calculation methods. Future studies are required to identify which methods are most sensitive to disc degeneration and repair in order to identify a “best” method. The neutral zone (NZ) is a clinically relevant metric of spinal motion segment laxity, but measuring it is difficult due to the viscoelastic nature of the intervertebral disc. Various NZ quantification methods are currently used in the field, yet the degree of agreeability and interchangeability between methods remains unknown. Our findings indicate that methods rarely agree in measurement and should therefore not be considered interchangeable, highlighting the need to clearly describe the underlying methodology in order to contextualize NZ results.

Background and aims Root biomass is one of the most widely used parameters to characterise root growth and belowground carbon stock. Our aim was to define a standard method to estimate the root biomass of young and adult oil palm trees in commercial plantations. Methods Three methods based on the sampling excavation volume were compared using the same sampled tree. Work time and the number of workers required for each operation were recorded. We compared two large excavation volumes based on Voronoi tessellation and the standard root auger coring method in one 2-year-old and one 16-year-old commercial oil-palm plantation in Benin, West Africa. Results Oil palm total root biomass was estimated at 0.84 and 22.23 Mg ha −1 in the 2-year-old and 16-year-old plantation, respectively. Compared to the reference method, the simplified Voronoi trench method estimated slightly higher (+5%) and lower (−17%) total root biomass with no significant differences but required 2 and 3 times more labour time, respectively, while the auger method estimated significantly lower (−23% and − 53%) total root biomass in the 2-year-old and 16-year-old plantation, respectively. Coarse and fine root biomass were significantly higher under the windrow than under the footpath zones. Conclusion The simplified Voronoi trench method required twice as much labour time as the auger method but was most efficient way to estimate oil palm total root biomass, irrespective of the age of the plantation.

Introduction Cellular bone matrices (CBM) are allograft products that provide three components essential to new bone formation: an osteoconductive scaffold, extracellular growth factors for cell proliferation and differentiation, and viable cells with osteogenic potential. This is an emerging technology being applied to augment spinal fusion procedures as an alternative to autografts. Methods We aim to compare the ability of six commercially‐available human CBMs (Trinity ELITE®, ViviGen®, Cellentra®, Osteocel® Pro, Bio4® and Map3®) to form a stable spinal fusion using an athymic rat model of posterolateral fusion. Iliac crest bone from syngeneic rats was used as a control to approximate the human gold standard. The allografts were implanted at L4‐5 according to vendor specifications in male athymic rats, with 15 rats in each group. MicroCT scans were performed at 48 hours and 6 weeks post‐implantation. The rats were euthanized 6 weeks after surgery and the lumbar spines were harvested for X‐ray, manual palpation and histology analysis by blinded reviewers. Results By manual palpation, five of 15 rats of the syngeneic bone group were fused at 6 weeks. While Trinity ELITE had eight of 15 and Cellentra 11 of 15 rats with stable fusion, only 2 of 15 of ViviGen‐implanted spines were fused and zero of 15 of the Osteocel Pro, Bio4 and Map3 produced stable fusion. MicroCT analysis indicated that total bone volume increased from day 0 to week 6 for all groups except syngeneic bone group. Trinity ELITE (65%) and Cellentra (73%) had significantly greater bone volume increases over all other implants, which was consistent with the histological analysis. Conclusion Trinity ELITE and Cellentra were significantly better than other implants at forming new bone and achieving spinal fusion in this rat model at week 6. These results suggest that there may be large differences in the ability of different CBMs to elicit a successful fusion in the posterolateral spine. We aim to compare the ability of six commercially‐available human CBMs (Trinity ELITE, ViviGen, Cellentra, Osteocel Pro, Bio4 and Map3) to form a stable spinal fusion using an athymic rat model of posterolateral fusion. Our results showed that Trinity ELITE and Cellentra were significantly better than other implants at forming new bone and achieving spinal fusion in this rat model at week 6.

Background and Aims Nursing home research may involve eliciting information from managers, yet response rates for Directors of Nursing have not been recently studied. As a part of a more extensive study, we surveyed all nursing homes in three states in 2018 and 2019, updating how to survey these leaders effectively. We focus on response rates as a measure of non‐response error and comparison of nursing home's characteristics to their population values as a measure of representation error. Methods We surveyed Directors of Nursing or their designees in nursing homes serving adult residents with at least 30 beds in California, Massachusetts, and Ohio (N = 2389). We collected contact information for respondents and then emailed survey invitations and links, followed by three email reminders and a paper version. Nursing home associations in two of the states contacted their members on our behalf. We compared the response rates across waves and states. We also compared the characteristics of nursing homes based on whether the response was via email or paper. In a multivariable logit regression, we used characteristics of the survey and the nursing homes to predict whether their DON responded to the survey using adjustments for multiple comparisons. Results The response rate was higher for the first wave than for the second (30% vs 20.5%). The highest response rate was in Massachusetts (31.8%), followed by Ohio (25.8%) and California (19.5%). Nursing home characteristics did not vary by response mode. Additionally, we did not find any statistically significant predictors of whether a nursing home responded. Conclusion A single‐mode survey may provide a reasonably representative sample at the cost of sample size. With that said, however, switching modes can increase sample size without potentially biasing the sample.

Circular data are common in biological studies. The most fundamental question that can be asked of a sample of circular data is whether it suggests that the underlying population is uniformly distributed around the circle, or whether it is concentrated around at least one preferred direction (e.g. a migratory goal or activity phase). We compared the statistical power of five commonly used tests (the Rayleigh test, the V-test, Watson's test, Kuiper's test and Rao's spacing test) across a range of different unimodal scenarios. The V-test showed higher power for symmetrical distributions, Rao's spacing performed worst for all explored unimodal distributions tested and the remaining three tests showed very similar performance. However, the V-test only applies if the hypothesis is restricted to one (pre-specified) direction of interest. In all other unimodal cases, we recommend using the Rayleigh test. Much less explored is the multimodal case with data concentrated around several directions. We performed power simulations for a variety of multimodal situations, testing the performance of the widely used Rayleigh, Rao's, Watson, and Kuiper's tests as well as the more recent Bogdan and Hermans-Rasson tests. Our analyses of alternative statistical methods show that the commonly used tests lack statistical power in many of multimodal cases. Transformation of the raw data (e.g. doubling the angles) can overcome some of the issues, but only in the case of perfect f-fold symmetry. However, the Hermans-Rasson method, which is not yet implemented in any software package, outcompetes the alternative tests (often by substantial margins) in most of the multimodal situations explored. We recommend the wider uptake of the powerful but hitherto neglected Hermans-Rasson method. In summary, we provide guidance for biologists helping them to make decisions when testing circular data for single or multiple departures from uniformity.

Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1 , IDH2 , TP53 , H3F3A, and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within 6 h and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas, and brain metastases of different primary sites. Single nucleotide variants in IDH1 , IDH2, and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations, and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource-restricted settings.

Backgrounds and aims This article develops a Specialty Intensity Score, which uses patient diagnosis codes to estimate the number of specialist physicians a patient will need to access. Conceptually, the score can serve as a proxy for a patient's need for care coordination across doctors. Such a measure may be valuable to researchers studying care coordination practices for complex patients. In contrast with previous comorbidity scores, which focus primarily on mortality and utilization, this comorbidity score approximates the complexity of a patient's the interaction with the health care system. Methods We use 2015 inpatient claims data from the Centers for Medicare and Medicaid Services to model the relationship between a patient's diagnoses and physician specialty usage. We estimate usage of specialist doctors by using a least absolute shrinkage and selection operator Poisson model. The Specialty Intensity Score is then constructed using this predicted specialty usage. To validate our score, we test its power to predict the occurrence of patient safety incidents and compare that with the predictive power of the Charlson comorbidity index. Results Our model uses 127 of the 279 International Classification of Disease, 10th Revision, Clinical Modification (ICD‐10‐CM) diagnosis subchapters to predict specialty usage, thus creating the Specialty Intensity Score. This score has significantly greater power in predicting patient safety complications than the widely used Charlson comorbidity index. Conclusion The Specialty Intensity Score developed in this article can be used by health services researchers and administrators to approximate a patient's need for care coordination across multiple specialist doctors. It, therefore, can help with evaluation of care coordination practices by allowing researchers to restrict their analysis of outcomes to the patients most impacted by those practices.

Proper interpretation of analytical ultracentrifugation (AUC) data for purified proteins requires ancillary information and calculations to account for factors such as buoyancy, buffer viscosity, hydration, and temperature. The utility program SEDNTERP has been widely used by the AUC community for this purpose since its introduction in the mid-1990s. Recent extensions to this program (1) allow it to incorporate data from diffusion as well as AUC experiments; and (2) allow it to calculate the refractive index of buffer solutions (based on the solute composition of the buffer), as well as the specific refractive increment ( dn/dc ) of proteins based on their composition. These two extensions should be quite useful to the light scattering community as well as helpful for AUC users. The latest version also adds new terms to the partial specific volume calculations which should improve the accuracy, particularly for smaller proteins and peptides, and can calculate the viscosity of buffers containing heavy isotopes of water. It also uses newer, more accurate equations for the density of water and for the hydrodynamic properties of rods and disks. This article will summarize and review all the equations used in the current program version and the scientific background behind them. It will tabulate the values used to calculate the partial specific volume and dn/dc , as well as the polynomial coefficients used in calculating the buffer density and viscosity (most of which have not been previously published), as well as the new ones used in calculating the buffer refractive index.