Lessons learnt in photocatalysis - the influence of solvent polarity and the photostability of the photocatalyst.

Herein, we show that there is significant variation in both the triplet energies and redox properties of photocatalysts as a function of solvent based on a study of eight PCs in four solvents of varying polarity. A range of photocatalytic electron and energy transfer reactions were investigated using a subset of the PCs. For the photoredox reactions, the yields are not correlated with solvent polarity. Instead, when the PC could promote the formation of the target product, we observed photodegradation for all PCs across all solvents, something that is rarely investigated in the literature. This, therefore, makes it difficult to ascertain whether the parent PC and/or the photodegraded product is responsible for the photochemistry, or indeed, whether photodegradation is actually detrimental to the reaction yield. Conversely, the PCs were found to be photostable for energy transfer reactions; however, yields were not correlated to the triplet energies of the PCs, highlighting that triplet energies alone are not a suitable descriptor to discriminate the performance between PCs in photoinduced energy transfer processes.

The accuracy of digital templating in the preoperative planning of total knee arthroplasties: A systematic review and meta-analysis.

AIMS: Accurately predicting the implant size in total knee arthroplasties could increase the efficiency of the operation, decrease the costs associated with the procedure and result in improved patient outcomes. To substantiate its continued use, digital templating must demonstrate itself to be an accurate tool in predicting component size in order for surgeons to confidently use it to optimize the procedure. METHODS: A systematic literature review was performed and identified 16 studies within the Pubmed, Ebsco and Ovid-Embase databases, with 1189 TKR prostheses included for analysis. A quality of evidence assessment was performed on each study depending on the study design. A random effects meta-analysis model was used to pool overall implant accuracy and the reported inter-rater agreement when performing digital templating and displayed in a forest plot. Meta-regression was used analyze potential factors that may affect the accuracy of digital templating. RESULTS: The pooled proportion of accurate templates with 0 margin of error was found to be 56% (52-61, 95CI), which increases to 96% (0.94-0.98, 95CI) when allowing for a 1 size margin of error. Subgroup analysis between femoral and tibial components concluded no statistically significant difference. CONCLUSIONS: This study supports the continued use of digital templating for planning total knee arthroplasties and recommends further subgroup analysis of patient age, body mass index and sex against accuracy. This review was registered in the International Prospective Register of Systematic Reviews Database under ID: CRD420222367461. No funding was provided for the completion of this systematic review. BACKGROUND: Templating in the preoperative planning of total knee arthroplasties is a vital step in ensuring maximum operative efficiency. A method that can accurately predict the required implant size within 1 size could improve theatre turnover, decrease costs and benefit patient outcomes. The current literature on the accuracy of digital templating in total knee arthroplasties lacks a systematic review calculating the overall accuracy of the process, this study aims to address this gap.

An Unusual Presentation of SCAD in a Young Male Soldier.

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction and sudden cardiac death in young individuals without significant cardiovascular risk factors. The etiology of SCAD appears to be multifactorial and is often precipitated by physical and emotional stress superimposed on underlying arteriopathy, connective tissue disorders, systemic inflammatory disorders, genetic factors, and hormonal influences. There are no current societal guidelines to stratify young soldiers' risk of developing SCAD. Diagnosis typically requires invasive coronary artery angiography which is largely unavailable in stations with limited medical resources. Furthermore, young patients with SCAD often present with atypical cardiac symptoms, such as heartburn leading to the misdiagnosis of gastroesophageal reflux disease and a delay in diagnosis and management. We present a 21-year-old active duty male who was transferred from Okinawa, Japan to a tertiary military medical center for evaluation of hypercoagulable conditions after CT revealed non-obstructing portal venous thrombosis extending to right hepatic vein, splenic vein thrombosis with splenic infarct, and bilateral wedge-shaped renal infarct. Extensive work-up ultimately revealed mid-left anterior descending spiral dissection with transmural infarct of inferior, anteroseptal, and inferoseptal wall resulting in the formation of left ventricular thrombus, subsequently causing thromboembolism to multiple organs. This case demonstrates the ramifications of SCAD when diagnosis and management are delayed and serve as a poignant reminder for all providers to include SCAD in the differential diagnosis for young soldiers with atypical chest pain.

The Role of Strength-Related Factors on Psychological Readiness for Return to Sport Following Anterior Cruciate Ligament (ACL) Reconstruction.

Psychological readiness following anterior cruciate ligament reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between anterior cruciate ligament return to sport after injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7 ± 2.5 years old; 174.2 ± 7.5 cm; 70.2 ± 8.5 kg; 18.2 ± 8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°·s-1 and 180°·s-1). Based on ACL-RSI scores, they were divided into "cases" and "controls", deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps' and hamstrings' rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls, cases showed significantly lower quadriceps torque at angles close to full knee extension (40 deg and 30 deg from extension). They also showed lower RTD than controls, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes' return to sport (RTS) by focusing on the restoration of RTD and strength at angles close to full knee extension.

Cashew-Induced Oxalate Nephropathy: A Rare Cause of Acute Renal Failure.

We present a rare case of cashew-induced oxalate nephropathy in a 69 year old veteran male with history of type 2 diabetes mellitus, nephrolithiasis, and undiagnosed chronic kidney disease (CKD). Oxalate nephropathy is a rare cause of acute renal failure with poor prognosis. The various causes of oxalate nephropathy are categorized as primary or secondary hyperoxaluria. Primary hyperoxaluria is caused by genetic mutation in genes involved in the metabolism of glyoxylate. Secondary hyperoxaluria is caused by mal-absorptive state, excessive intake of oxalate-rich diet, inflammatory diseases, and medications such as orlistat and antibiotics. Diet-induced oxalate nephropathy is often identified after unexplained acute kidney injury in patients with underlying CKD. Definitive diagnosis requires renal biopsy as laboratory tests are non-specific. A simple dietary history in CKD patients during routine primary care visit may lead to early diagnosis and lead to prevention of acute renal failure and progression of renal disease.

Identification of the Key Parameters for Horizontal Transition Dipole Orientation in Fluorescent and TADF Organic Light-Emitting Diodes.

In organic light-emitting diodes (OLEDs), horizontal orientation of the emissive transition dipole moment (TDM) can improve light outcoupling efficiency by up to 50% relative to random orientation. Therefore, there have been extensive efforts to identify drivers of horizontal orientation. The aspect ratio of the emitter molecule and the glass-transition temperature (Tg ) of the films are currently regarded as particularly important. However, there remains a paucity of systematic studies that establish the extent to which these and other parameters control orientation in the wide range of emitter systems relevant for state-of-the-art OLEDs. Here, recent work on molecular orientation of fluorescent and thermally activated delayed fluorescent emitters in vacuum-processed OLEDs is reviewed. Additionally, to identify parameters linked to TDM orientation, a meta-analysis of 203 published emitter systems is conducted and combined with density-functional theory calculations. Molecular weight (MW) and linearity are identified as key parameters in neat systems. In host-guest systems with low-MW emitters, orientation is mostly influenced by the host Tg , whereas the length and MW of the emitter become more relevant for systems involving higher-MW emitters. To close, a perspective of where the field must advance to establish a comprehensive model of molecular orientation is given.

Quantification of Opioid Prescription Practice Changes Due to Hydrocodone Combination Product Rescheduling in an Academic Pain Clinic.

PURPOSE: To determine the effect of rescheduling on prescription practices in a large academic hospital-based multidisciplinary practice comprising anesthesiologist-trained pain physicians. PATIENTS AND METHODS: We examined the number of HCP prescriptions written and quantity of tablets prescribed during a 6-month period prior to rescheduling and compared this with a 6-month period 1 year after rescheduling. We also examined the changes in prescription of tramadol and acetaminophen with codeine from one period to the next. RESULTS: Our pain clinic conducted 3,320 office visits during the 6-month period prior to HCP rescheduling and 6,003 office visits in the 6-month period 1 year after rescheduling. The charted data from each of these visits were used for our analysis. The mean number of tablets of HCPs prescribed per patient decreased from 318.48 in the pre-period to 242.27 tablets in the post-period, while the mean number of HCP prescriptions per patient decreased from 2.24 to 1.84. The mean number of acetaminophen with codeine tablets prescribed per patient increased from 3.46 to 15.27 in the pre- and post-period. Similarly, the mean number of tramadol tablets per patient increased from 47.33 to 61.97 in the pre- and post-period. The mean number of acetaminophen with codeine and tramadol prescriptions per patient increased from 0.02 to 0.15 and 0.38 to 0.51 in the pre- and post-period, respectively. In the 6-month post-period, fewer new patients were started on opioids compared to the 6-month pre-period, 16% and 27%, respectively. CONCLUSION: Our study showed a significant decrease in the mean number of HCP prescriptions written per patient, as well as a decrease in the mean number of HCP tablets prescribed. Pain physicians in our clinic increased the number of prescriptions for the non-HCPs. The number of acetaminophen with codeine and tramadol tablets prescribed significantly increased. Therefore, the rescheduling of HCPs has profoundly impacted practices within this academic pain clinic.

Modelling cyclists' comfort zones from obstacle avoidance manoeuvres.

This paper introduces a framework for modelling the cyclist's comfort zone. Unlike the driver's comfort zone, little is known about the cyclist's. The framework draws on existing literature in cognitive science about driver behaviour to explain experimental results from cycling field trials, and the modelling of these results. We modelled braking and steering manoeuvres from field data of cyclists' obstacle avoidance within their comfort zone. Results show that when cyclists avoided obstacles by braking, they kept a constant deceleration; as speed increased, they started to brake earlier, farther from the obstacle, maintaining an almost constant time to collision. When cyclists avoided obstacles by steering, they maintained a constant distance from the object, independent of speed. Overall, the higher the speed, the more the steering manoeuvres were temporally delayed compared to braking manoeuvres. We discuss these results and other similarities between cyclist and driver behaviour during obstacle avoidance. Implications for the design of acceptable active safety and infrastructure design are also addressed.

Statistical design of noninferiority multiple region clinical trials to assess global and consistent treatment effects.

Noninferiority multiregional clinical trials (MRCTs) have recently received increasing attention in drug development. While a major goal in an MRCT is to estimate the global treatment effect, it is also important to assess the consistency of treatment effects across multiple regions. In this paper, we propose an intuitive definition of consistency of noninferior treatment effects across regions under the random-effects modeling framework. Specifically, we quantify the consistency of treatment effects by the percentage of regions that meet a predefined treatment margin. This new approach enables us to achieve both goals in one modeling framework. We propose to use a signed likelihood ratio test for testing the global treatment effect and the consistency of noninferior treatment effects. In addition, we provide guidelines for the allocation rule to achieve optimal power for testing consistency among multiple regions. Extensive simulation studies are conducted to examine the performance of the proposed methodology. An application to a real data example is provided.

Tissue Classification Using Optical Spectroscopy Accurately Differentiates Cancer and Chronic Pancreatitis.

OBJECTIVES: Current pancreatic cancer diagnostics cannot reliably detect early disease or distinguish it from chronic pancreatitis. We test the hypothesis that optical spectroscopy can accurately differentiate cancer from chronic pancreatitis and normal pancreas. We developed and tested clinically compatible multimodal optical spectroscopy technology to measure reflectance and endogenous fluorescence from human pancreatic tissues. METHODS: Freshly excised pancreatic tissue specimens (39 normal, 34 chronic pancreatitis, 32 adenocarcinoma) from 18 patients were optically interrogated, with site-specific histopathology representing the criterion standard. A multinomial logistic model using principal component analysis and generalized estimating equations provided statistically rigorous tissue classification. RESULTS: Optical spectroscopy distinguished pancreatic cancer from normal pancreas and chronic pancreatitis (sensitivity, 91%; specificity, 82%; positive predictive value, 69%; negative predictive value, 95%; area under receiver operating characteristic curve, 0.89). Reflectance alone provided essentially the same classification accuracy as reflectance and fluorescence combined, suggesting that a rapid, low-cost, reduced-footprint, reflectance-based device could be deployed without notable loss of diagnostic power. CONCLUSIONS: Our novel, clinically compatible, label-free optical diagnostic technology accurately characterizes pancreatic tissues. These data provide the scientific foundation demonstrating that optical spectroscopy can potentially improve diagnosis of pancreatic cancer and chronic pancreatitis.

KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1.

KDM2B recruits H2A-ubiquitinating activity of a non-canonical Polycomb Repression Complex 1 (PRC1.1) to CpG islands, facilitating gene repression. We investigated the molecular basis of recruitment using in vitro assembly assays to identify minimal components, subcomplexes, and domains required for recruitment. A minimal four-component PRC1.1 complex can be assembled by combining two separately isolated subcomplexes: the DNA-binding KDM2B/SKP1 heterodimer and the heterodimer of BCORL1 and PCGF1, a core component of PRC1.1. The crystal structure of the KDM2B/SKP1/BCORL1/PCGF1 complex illustrates the crucial role played by the PCGF1/BCORL1 heterodimer. The BCORL1 PUFD domain positions residues preceding the RAWUL domain of PCGF1 to create an extended interface for interaction with KDM2B, which is unique to the PCGF1-containing PRC1.1 complex. The structure also suggests how KDM2B might simultaneously function in PRC1.1 and an SCF ubiquitin ligase complex and the possible molecular consequences of BCOR PUFD internal tandem duplications found in pediatric kidney and brain tumors.

PRISM: Phase 2 trial with panitumumab monotherapy as second-line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer (PRISM) trial evaluated the safety and efficacy of panitumumab as second-line monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: This was an open-label, single-arm, multicenter trial that enrolled patients with progressive disease or intolerance to first-line systemic chemotherapy for recurrent or metastatic SCCHN. Patients received panitumumab 9 mg/kg Q3W. The primary endpoint was overall response rate; secondary endpoints included disease control rate, overall survival (OS), progression-free survival (PFS), and safety. RESULTS: The overall response rate was 4% (2 of 51 patients) and the disease control rate was 39% (20 of 51 patients). Median PFS was 1.4 months (95% confidence interval [CI] = 1.3-2.4 months). Median OS was 5.1 months (95% CI = 4.3-8.3 months). The most common adverse events were rash/dermatitis acneiform (69%), fatigue (33%), dry skin (21%), and hypomagnesemia (21%). There was one treatment-related death (angioedema). CONCLUSION: Panitumumab monotherapy had limited activity in previously treated patients with recurrent or metastatic SCCHN. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1756-E1761, 2016.

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced Apc(Min/+) mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc(Min/+) mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30-40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc(Min/+) mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc(Min/+) mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.

Aspiration pneumonia after chemo-intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors.

BACKGROUND: The purpose of this study was to assess aspiration pneumonia (AsPn) rates and predictors after chemo-irradiation for head and neck cancer. METHODS: The was a prospective study of 72 patients with stage III to IV oropharyngeal cancer treated definitively with intensity-modulated radiotherapy (IMRT) concurrent with weekly carboplatin and paclitaxel. AsPn was recorded prospectively and dysphagia was evaluated longitudinally through 2 years posttherapy by observer-rated (Common Toxicity Criteria version [CTCAE]) scores, patient-reported scores, and videofluoroscopy. RESULTS: Sixteen patients (20%) developed AsPn. Predictive factors included T classification (p = .01), aspiration detected on videofluoroscopy (videofluoroscopy-asp; p = .0007), and patient-reported dysphagia (p = .02-.0003), but not observer-rated dysphagia (p = .4). Combining T classification, patient reported dysphagia, and videofluoroscopy-asp, provided the best predictive model. CONCLUSION: AsPn continues to be an under-reported consequence of chemo-irradiation for head and neck cancer. These data support using patient-reported dysphagia to identify high-risk patients requiring videofluoroscopy evaluation for preventive measures. Reducing videofluoroscopy-asp rates, by reducing swallowing structures radiation doses and by trials reducing treatment intensity in patients predicted to do well, are likely to reduce AsPn rates.

Concurrent whole brain radiotherapy and bortezomib for brain metastasis.

BACKGROUND: Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. METHODS: A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. RESULTS: Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). CONCLUSIONS: Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment.

Stereotactic body radiation therapy for primary and metastatic liver tumors.

OBJECTIVES: The full potential of stereotactic body radiation therapy (SBRT), in the treatment of unresectable intrahepatic malignancies, has yet to be realized as our experience is still limited. Thus, we evaluated SBRT outcomes for primary and metastatic liver tumors, with the goal of identifying factors that may aid in optimization of therapy. METHODS: From 2005 to 2010, 62 patients with 106 primary and metastatic liver tumors were treated with SBRT to a median biologic effective dose (BED) of 100 Gy (42.6-180). The majority of patients received either three (47%) or five fractions (48%). Median gross tumor volume (GTV) was 8.8 cm(3) (0.2-222.4). RESULTS: With a median follow-up of 18 months (0.46-46.8), freedom from local progression (FFLP) was observed in 97 of 106 treated tumors, with 1- and 2-year FFLP rates of 93% and 82%. Median overall survival (OS) for all patients was 25.2 months, with 1- and 2-year OS of 81% and 52%. Neither BED nor GTV significantly predicted for FFLP. Local failure was associated with a higher risk of death [hazard ratio (HR) = 5.1, P = .0007]. One Child-Pugh Class B patient developed radiation-induced liver disease. There were no other significant toxicities. CONCLUSIONS: SBRT provides excellent local control for both primary and metastatic liver lesions with minimal toxicity. Future studies should focus on appropriate selection of patients and on careful assessment of liver function to maximize both the safety and efficacy of treatment.

Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics.

PURPOSE: There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI) to examine regional variation in white matter changes following chemoradiotherapy. METHODS: Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT) ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest. RESULTS: Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05), with the largest changes (20-50%) in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001). The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385). CONCLUSIONS: Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.

Permutation tests for random effects in linear mixed models.

Inference regarding the inclusion or exclusion of random effects in linear mixed models is challenging because the variance components are located on the boundary of their parameter space under the usual null hypothesis. As a result, the asymptotic null distribution of the Wald, score, and likelihood ratio tests will not have the typical χ(2) distribution. Although it has been proved that the correct asymptotic distribution is a mixture of χ(2) distributions, the appropriate mixture distribution is rather cumbersome and nonintuitive when the null and alternative hypotheses differ by more than one random effect. As alternatives, we present two permutation tests, one that is based on the best linear unbiased predictors and one that is based on the restricted likelihood ratio test statistic. Both methods involve weighted residuals, with the weights determined by the among- and within-subject variance components. The null permutation distributions of our statistics are computed by permuting the residuals both within and among subjects and are valid both asymptotically and in small samples. We examine the size and power of our tests via simulation under a variety of settings and apply our test to a published data set of chronic myelogenous leukemia patients.

Development and validation of a quantitative real-time polymerase chain reaction classifier for lung cancer prognosis.

INTRODUCTION: This prospective study aimed to develop a robust and clinically applicable method to identify patients with high-risk early-stage lung cancer and then to validate this method for use in future translational studies. METHODS: Three published Affymetrix microarray data sets representing 680 primary tumors were used in the survival-related gene selection procedure using clustering, Cox model, and random survival forest analysis. A final set of 91 genes was selected and tested as a predictor of survival using a quantitative real-time polymerase chain reaction-based assay using an independent cohort of 101 lung adenocarcinomas. RESULTS: The random survival forest model built from 91 genes in the training set predicted patient survival in an independent cohort of 101 lung adenocarcinomas, with a prediction error rate of 26.6%. The mortality risk index was significantly related to survival (Cox model p < 0.00001) and separated all patients into low-, medium-, and high-risk groups (hazard ratio = 1.00, 2.82, 4.42). The mortality risk index was also related to survival in stage 1 patients (Cox model p = 0.001), separating patients into low-, medium-, and high-risk groups (hazard ratio = 1.00, 3.29, 3.77). CONCLUSIONS: The development and validation of this robust quantitative real-time polymerase chain reaction platform allows prediction of patient survival with early-stage lung cancer. Utilization will now allow investigators to evaluate it prospectively by incorporation into new clinical trials with the goal of personalized treatment of patients with lung cancer and improving patient survival.

A genetic linkage map of the vervet monkey (Chlorocebus aethiops sabaeus).

The spectacular progress in genomics increasingly highlights the importance of comparative biology in biomedical research. In particular, nonhuman primates, as model systems, provide a crucial intermediate between humans and mice. The close similarities between humans and other primates are stimulating primate studies in virtually every area of biomedical research, including development, anatomy, physiology, immunology, and behavior. The vervet monkey (Chlorocebus aethiops sabaeus) is an important model for studying human diseases and complex traits, especially behavior. We have developed a vervet genetic linkage map to enable mapping complex traits in this model organism and facilitate comparative genomic analysis between vervet and other primates. Here we report construction of an initial genetic map built with about 360 human orthologous short tandem repeats (STRs) that were genotyped in 434 members of an extended vervet pedigree. The map includes 226 markers mapped in a unique order with a resolution of 9.8 Kosambi centimorgans (cM) in the vervet monkey genome, and with a total length (including all 360 markers) of 2726 cM. At least one complex and 11 simple rearrangements in marker order distinguish vervet chromosomes from human homologs. While inversions and insertions can explain a similar number of changes in marker order between vervet and rhesus homologs, mostly inversions are observed when vervet chromosome organization is compared to that in human and chimpanzee. Our results support the notion that large inversions played a less prominent role in the evolution within the group of the Old World monkeys compared to the human and chimpanzee lineages.