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Cognitive control (CC) is a vital component of cognition associated with problem-solving in everyday life. Many neurological and neuropsychiatric conditions have deficits associated with CC. CC is composed of multiple behaviors including switching, inhibiting, and updating. The fronto-parietal control network B (FPCN-B), the dorsal attention network (DAN), the cingulo-opercular network (CON) and the dorsal default-mode network (dorsal-DMN) have been associated with switching and inhibiting behaviors. However, our understanding of how these brain regions interact to bring about CC behaviors is still unclear. In the current study, participants performed two in-scanner tasks that required switching and inhibiting. We then used a series of support vector regression (SVR) models containing individually-estimated functional connectivity between the networks of interest derived during tasks and at rest to predict inhibition and switching behaviors in individual subjects. We observed that the combination of between-network connectivity from these individually estimated functional networks predicted accurate and timely inhibition and switching behaviors in individuals. We also observed that the relationships between canonical task-positive and task-negative networks predicted inhibiting and switching behaviors. Finally, we observed a functional dissociation between the FPCN-A and FPCNB during rest, and task performance predicted inhibiting and switching behaviors. These results suggest that individually estimated networks can predict individual CC behaviors, that between-network functional connectivity estimated within individuals is vital to understanding how CC arises, and that the fractionation of the FPCN and the DMN may be associated with different behaviors than their canonically accepted behaviors.

In the era of "big data", we are gaining rich person-specific information about neuroanatomy, neural function, and cognitive functions. However, the optimal ways to create precise approaches to optimize individuals' mental functions in health and disease are unclear. Multimodal analysis and modeling approaches can guide neuromodulation by combining anatomical networks, functional signal analysis, and cognitive neuroscience paradigms in single subjects. Our progress could be improved by progressing from statistical fits to mechanistic models. Using transcranial magnetic stimulation as an example, we discuss how integrating methods with a focus on mechanisms could improve our predictions TMS effects within individuals, refine our models of health and disease, and improve our treatments.

Transcranial magnetic stimulation (TMS) is used in several FDA-approved treatments and, increasingly, to treat neurological disorders in off-label uses. However, the mechanism by which TMS causes physiological change is unclear, as are the origins of response variability in the general population. Ideally, objective in vivo biomarkers could shed light on these unknowns and eventually inform personalized interventions. Continuous theta burst stimulation (cTBS) is a form of TMS which has been observed to reduce motor evoked potentials (MEPs) for 60 minutes or longer post-stimulation, although the consistency of this effect and its mechanism continue to be under debate. Here, we use glutamate-weighted chemical exchange saturation transfer (gluCEST) magnetic resonance imaging (MRI) at ultra-high magnetic field (7T) to measure changes in glutamate concentration at the site of cTBS. We find that gluCEST signal in the ipsilateral hemisphere of the brain generally decreases in response to cTBS, whereas consistent changes were not detected in the contralateral or in subjects receiving a sham stimulation.One Sentence SummaryWe used glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) imaging to detect changes in glutamate contrast in the brains of young, healthy adults undergoing transcranial magnetic stimulation (TMS) to the motor cortex.

Aphasia is one of the most prevalent cognitive syndromes caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion size and extent obfuscates the links between the local effects of the lesion, global anatomical network organization, and aphasia symptoms. We applied a simulated attack approach to examine the effects of 39 stroke lesions on network topology by simulating their effects in a control sample of 36 healthy brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores (the Western Aphasia Battery Aphasia Quotient; WAB-AQ), four behavioral factor scores obtained from a neuropsychological battery, and a factor sum), we compared the behavioral variance accounted for by simulated post-stroke connectomes to that observed in the randomly permuted data. Overall, global measures of network topology in the whole brain and left hemisphere accounted for 10% variance or more of the WAB-AQ and the lexical factor score beyond lesion volume and null permutations. Streamline networks provided more reliable point estimates than FA networks. Edge weights and network efficiency were weighted most highly in predicting the WAB-AQ for FA networks. Overall, our results suggest that global network measures can provide modest statistical value predicting overall aphasia severity, but less value in predicting specific behaviors. Variability in estimates could be induced by premorbid ability, deafferentation and diaschisis, and neuroplasticity following stroke.

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti(3)C(2) MXene (a two-dimensional transition metal carbide nanomaterial) and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials, and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in applications ranging from mapping large scale neuromuscular networks in humans to cortical neural recording and microstimulation in swine and rodent models. Finally, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.

The severity of post-stroke aphasia is related to damage to white matter connections. However, neural signaling can route not only through direct connections, but also along multi-step network paths. When brain networks are damaged by stroke, paths can bypass around the damage to restore communication. The shortest network paths between regions could be the most efficient routes for mediating bypasses. We examined how shortest-path bypasses after left hemisphere strokes were related to language performance. Regions within and outside of the canonical language network could be important in aphasia recovery. Therefore, we innovated methods to measure the influence of bypasses in the whole brain.Distinguishing bypasses from all residual shortest paths is difficult without pre-stroke imaging. We identified bypasses by finding shortest paths in subjects with stroke that were longer than those observed in the average network of the most reliably observed connections in age-matched controls. We tested whether features of those bypasses predicted scores in four orthogonal dimensions of language performance derived from a factor analysis of a battery of language tasks. The features were the length of each bypass in steps, and how many bypasses overlapped on each individual direct connection. We related these bypass features to language factors using grid-search cross-validated Support Vector Regression, a technique that extracts robust relationships in high-dimensional data analysis.We discovered that the length of bypasses reliably predicted variance in lexical production (R2= .576) and auditory comprehension scores (R2= .164). Bypass overlaps reliably predicted variance in Lexical Production scores (R2 = .247). The predictive elongation features revealed that bypass efficiency along the dorsal stream and ventral stream were most related to Lexical Production and Auditory Comprehension, respectively. Among the predictive bypass overlaps, increased bypass routing through the right hemisphere putamen was negatively related to lexical production ability.

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a novel class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti3C2 MXene and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials, and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in a number of applications ranging from mapping large scale neuromuscular networks in humans to delivering cortical microstimulation in small animal models. Finally, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.

Background: There is currently little evidence regarding the use of medical cannabis for the treatment of intractable pain. Literature published on the subject to date has yielded mixed results concerning the efficacy of medical cannabis and has been limited by study design and regulatory issues. Objective: The objective of this study was to determine if the use of medical cannabis affects the amount of opioids and benzodiazepines used by patients on a daily basis. Methods: This single-center, retrospective cohort study evaluated opioid and benzodiazepine doses over a 6-month time period for patients certified to use medical cannabis for intractable pain. All available daily milligram morphine equivalents (MMEs) and daily diazepam equivalents (DEs) were calculated at baseline and at 3 and 6 months. Results: A total of 77 patients were included in the final analysis. There was a statistically significant decrease in median MME from baseline to 3 months (−32.5 mg; P = 0.013) and 6 months (−39.1 mg; P = 0.001). Additionally, there was a non–statistically significant decrease in median DE at 3 months (−3.75 mg; P = 0.285) and no change in median DE from baseline to 6 months (−0 mg; P = 0.833). Conclusion and Relevance: Over the course of this 6-month retrospective study, patients using medical cannabis for intractable pain experienced a significant reduction in the number of MMEs available to use for pain control. No significant difference was noted in DE from baseline. Further prospective studies are warranted to confirm or deny the opioid-sparing effects of medical cannabis when used to treat intractable pain.

Research based on construal level theory (CLT) suggests that thinking about the distant future can prime people to solve problems by insight (i.e., an "aha" moment) while thinking about the near future can prime them to solve problems analytically. In this study, we used a novel method to elucidate the time-course of temporal priming effects on creative problem solving. Specifically, we used growth-curve analysis (GCA) to examine the time-course of priming while participants solved a series of brief verbal problems. Participants were tested in two counterbalanced sessions in a within-subject experimental design; one session featured near-future priming and the other featured far-future priming. Our results suggest high-level construal may temporarily enhance analytical thinking; far-future priming caused transient facilitation of analytical solving while near-future priming induced weaker, transient facilitation of insightful solving. However, this effect is short-lived; priming produced no significant differences in the total number of insights and analytical solutions. Given the fleeting nature of these effects, future studies should consider implementing methodology that allows for aspects of the time-course of priming effects to be examined. A method such as GCA may reveal mild effects that would be otherwise missed using other types of analyses.

Jorge, Jose Antonio and Maria don’t know one another. They come from distinct backgrounds, but their stories intersect at the US–Mexico border and with the largest police force in the United States, and perhaps the world—US Customs and Border Protection (CBP). Their stories are representative of the human cost exacted by enforcement-only responses to human migration on the US-Mexico border that doubled the size of CBP in less than a decade without commensurate investment in oversight. The US government’s reluctance to hold border agents accountable to professional, 21st century police best practices that protect the paramount value of human life and promote bias-free, transparent policing has undermined both human rights and the agency’s mission by enabling widespread abuse and corruption.

Bilateral patent ductus arteriosus and isolated right pulmonary artery (RPA) is a rare anomaly often interpreted as congenital absence of the RPA. Recognized early, continuity between the main pulmonary artery and distal RPA can be established and long-term sequelae avoided. We report 2 patients who underwent neonatal repair using a nonvalved pulmonary artery allograft conduit placed anterior to the aorta to establish continuity between the main pulmonary artery and RPA. Both patients continue to do well 10 and 15 years postoperatively with good growth of the distal RPA and good exercise tolerance. This approach offers good long-term palliation.

In recent studies, we and others showed that autophagy is critical to estrogen receptor positive (ER+) breast cancer cell survival and the development of antiestrogen resistance. Consequently, new approaches are warranted for targeting autophagy in breast cancer cells undergoing antiestrogen therapy. Because crosstalk has been demonstrated between the autophagy- and proteasome-mediated pathways of protein degradation, this study investigated how the proteasome inhibitor bortezomib affects autophagy and cell survival in antiestrogen-treated ER+ breast cancer cells. Bortezomib, at clinically achievable doses, induced a robust death response in ER+, antiestrogen-sensitive and antiestrogen-resistant breast cancer cells undergoing hormonal therapy. Cleavage of PARP and lamin A was detectable as a read-out of cell death, following bortezomib-induced mitochondrial dysfunction. Prior to induction of cell death, bortezomib-treated cells showed high levels of light chain 3 (LC3) and p62, two protein markers for autophagy. The accumulation of these proteins was due to bortezomib-mediated blockade of long-lived protein turnover during macroautophagy. This novel action of bortezomib was linked to its blockade of cathepsin-L activity, which is required for autolysosomal-mediated protein turnover in ER+ breast cancer cells. Further, bortezomib-treated breast cancer cells showed induction of the unfolded protein response, with upregulation of CH OP and GRP78. Bortezomib also induced high levels of the pro-apoptotic protein BNIP3. Knockdown of CH OP and/or BNIP3 expression via RNAi targeting significantly attenuated the death-promoting effects of bortezomib. Thus, bortezomib inhibits prosurvival autophagy, in addition to its known function in blocking the proteasome, and is cytotoxic to hormonally treated ER+ breast cancer cells. These findings indicate that combining a proteasome inhibitor like bortezomib with antiestrogen therapy may have therapeutic advantage in the management of early-stage breast cancer.

Background High-risk human papillomavirus (HPV) is the causative agent of cervical cancer. Among the high-risk types, infection with HPV 16 and 18 is associated with significantly higher risk of disease progression, and consequently these two types together cause approximately 70% of invasive cervical cancer worldwide. Identification of HPV 16 and HPV 18 can provide valuable information for risk stratification and clinical management of patients infected with these two types in both ASC-US triage and primary screening in women over age 30. It may also be valuable in the assessment of HPV vaccine efficacy. Abbott RealTime High Risk (HR) HPV is a recently developed test for the detection of 14 high-risk HPV types with the ability to concurrently identify HPV 16 and 18. Objective To evaluate the clinical performance of Abbott RealTime HR HPV test. Study design: Abbott RealTime HR HPV was evaluated with 253 cervical specimens obtained from patients with CIN 3 and 340 specimens from patients with cervical cancer to determine clinical sensitivity of the test and the prevalence of types 16 and 18. Additionally, 757 cervical specimens obtained from women 30 years of age or older with normal cytology in a general screening population were tested to determine high-risk HPV positivity rate. Results The Abbott RealTime HR HPV test detected 97.2% (246/253) of CIN 3 specimens and 98.5% (335/340) of cancer specimens. HPV 16 was the most prevalent type in both CIN 3 (72.8%) and cancer specimens (64.5%). HPV 16 and 18 combined were detected in 78.9% of high-risk HPV positive CIN 3 and 84.8% of high-risk HPV positive cancer specimens. In specimens from women 30 years of age or older with normal cytology in a screening population, the HPV positivity rate was 6.5% (49/757). Conclusions Abbott RealTime HR HPV is a highly sensitive test for detection of high-grade cervical disease and cancer. The HPV 16 and HPV 18 typing capability of the test offers the advantage of stratifying patients at greater risk of progression and may thus aid in better patient care and management.

Asymmetrical alpha activation in the prefrontal cortex (frontal asymmetry) in electroencephalography (EEG) has been related to eating behavior. Prior studies linked dietary restraint with right frontal asymmetry [1] and disinhibition with left frontal asymmetry [2]. The current study simultaneously assessed restrained eating and hedonic hunger (drive for food reward in the absence of hunger) in relation to frontal asymmetry. Resting-state EEG and measures of restrained eating (Revised Restraint Scale; RRS) and hedonic hunger (Power of Food Scale; PFS) were assessed in 61 non-obese adults. Individually, hedonic hunger predicted left asymmetry. However, PFS and RRS were correlated (r=0.48, p

Depression, anxiety, and substance use disorder are frequently seen in patients with chronic pain. Depression and anxiety are common in substance use disorder. It may be difficult to determine when the conditions are a primary problem or secondary to the treatment of the pain itself. A variety of pharmacologic interventions are reviewed. Antidepressants with a dual-mechanism action (serotonin and norepinephrine) tend to be most effective. Various psychological treatments may be indicated, such as cognitive behavioral therapy, couples therapy, or electroconvulsive therapy (ECT). Anxiety models such as phobic avoidance of pain or Post Traumatic Stress Disorder may be relevant in understanding the patient with pain. A variety of pharmacologic approaches may address anxiety in patients with chronic pain. Various psychological interventions to address the anxiety are also discussed, including biofeedback training and Eye Movement Desensitization Reprocessing.

The expression of chloroplast and mitochondrial genes depends on nucleus-encoded proteins, some of which control processing, stability, and/or translation of organellar RNAs. To test the specificity of one such RNA stability factor, we used two known Chlamydomonas reinhardtii nonphotosynthetic mutants carrying mutations in the Mcd1 nuclear gene (mcd1-1 and mcd1-2). We previously reported that these mutants fail to accumulate the chloroplast petD mRNA and its product, subunit IV of the cytochrome b 6/f complex, which is essential for photosynthesis. Such mutants are generally presumed to be gene specific but are not tested rigorously. Here, we have used microarray analysis to assess changes in chloroplast, mitochondrial, and nuclear RNAs, and since few other RNAs were significantly altered in these mutants, conclude that Mcd1 is indeed specifically required for petD mRNA accumulation. In addition, a new unlinked nuclear mutation was discovered in mcd1-2, which greatly reduced chloroplast atpA mRNA accumulation. Genetic analyses showed failure to complement mda1-ncc1, where atpA-containing transcripts are similarly affected (D. Drapier, J. Girard-Bascou, D.B. Stern, F.-A. Wollman [2002] Plant J 31: 687–697), and we have named this putative new allele mda1-2. We conclude that DNA microarrays are efficient and useful for characterizing the specificity of organellar RNA accumulation mutants.

Background. Group II phospholipase A 2 (PLA 2 ) enzymes, the rate controlling enzymes in arachidonic acid metabolism, have been well characterized and subdivided into secretory 14-kDa PLA 2 (sPLA 2 ) and cytoplasmic 85-kDa PLA 2 (cPLA 2 ). Previous research has demonstrated increased PLA 2 in colorectal tumors. The present study was performed to determine the effect of specific PLA2 inhibitors on the proliferation and induction of apoptosis of intestinal epithelial cells. Methods. A continuously proliferating rat small intestinal cell line (IEC-18) and a mouse colon cancer cell line (WB-2054-M 4 ) were utilized for these experiments. The cells were placed in microwells with serum-free or serum-supplemented media. The effects of serum on proliferation were then evaluated in the presence of the cPLA 2 inhibitor, methylarachidonyl fluorophosphate (MAFP), or the sPLA 2 inhibitor p -bromophenacyl bromide (BPB). The sPLA 2 and cPLA 2 protein was estimated by Western blotting. Proliferation of intestinal cells was quantitated by incorporation of [ 3 H]thymidine into DNA and PLA 2 activity was evaluated by quantitating arachidonic acid formation and prostaglandin E 2 production. Results. Western blotting of IEC-18 and WB-2054 cell protein demonstrated sPLA 2 and cPLA 2 enzyme in cells incubated in media containing 10% serum. Spontaneous DNA synthesis was present in both cell lines and serum consistently increased proliferation. In IEC-18 cells [ 3 H]thymidine incorporation stimulated by serum was inhibited by MAFP and BPB, while in the malignant cell line, proliferation was inhibited only by BPB. BPB, but not MAFP, produced a dose-dependent increase in apoptotic ratios in both cell lines. Arachidonic acid and PGE 2 formation, stimulated by serum, was inhibited by MAFP and BPB. Conclusions. A differential effect on intestinal cell mitogenesis was seen with different PLA 2 inhibitors. The sPLA 2 inhibitor, but not the cPLA 2 inhibitor, significantly inhibited [ 3 H]thymidine incorporation in the malignant cell line. This occurred with an induction of apoptosis. sPLA 2 inhibitors may be specific inhibitors of growth of malignant cells. The inhibition of arachidonic acid and PGE 2 production did not correlate with the inhibition of proliferation, suggesting that the two processes may be unrelated.

The displacement of a significant amount of diesel fuel with natural gas during large scale fracturing and drilling developments can be economically feasible in many cases with minor modifications to most diesel engines using dual fuel technology. Dual fuel describes the combination of a pressure and volume regulated stream of natural gas flowing through the engine intake and mixing with a reduced amount of injected diesel fuel in the engine to create power output that is nearly indistinguishable from using straight diesel fuel in high pressure fracturing pumps and other support equipment. Combining diesel fuel and natural gas in a dual fuel system reduces emissions of NOx, SOx, CO2, VOCs and particulates. Diesel fuel volume has been reduced by as much as 1,575 gallons per frac stage in field testing (63% of total fuel). Engine modification is with primarily bolt-on aftermarket and factory kits. Fuel savings vary depending on price and availability of the natural gas fuel source: LNG (liquid form) from existing liquefaction and/or storage infrastructure or CNG (gaseous form) from local distribution companies (LDC), and/or field gas or distribution gas pipeline systems. Learnings presented from field trials include a case history of frac jobs using CNG, LNG and other gas supply. Economic data is presented on the overall process. Recognition that availability of adequate CNG and LNG fuel supplies may be limiting expanded implementation of dual fuel technologies has prompted us to consider methods of making both fuel supplies more available to other industrial segments as well as the oil and gas industry.

Pain caused by disorders of movement is often chronic and severe and may not be alleviated by commercially available medications. In such cases, the use of a compounded formulation can provide relief, either as sole therapy or as part of a combination treatment regimen. In this report, we review the effects of compounded analgesic preparations on chronic severe pain like that produced by arthritis, neuropathy, or postpolio syndrome. Case reports are included, formulations are presented, and two patients (one of whom, RFM III, is a coauthor of this paper) with a painful movement disorder describe their response to custom compounded therapy.

Objectives Pulmonary artery stenosis is a potential complication after Norwood palliation for hypoplastic left heart syndrome. It is unclear whether the shunt type or position in the Norwood procedure is associated with the risk of the development of pulmonary artery stenosis. We examined the risk of pulmonary artery stenosis and the need for pulmonary artery intervention in children undergoing the Norwood procedure with either the right ventricle to pulmonary artery conduit or modified Blalock-Taussig shunt. Methods A retrospective review was performed of all patients who underwent the Norwood procedure from January 1, 2003, to September 1, 2011. The data from 100 patients were reviewed, including catheterization and echocardiographic data, right ventricle to pulmonary artery conduit (n = 67, right shunt position in 17 and left in 50), and right ventricle to pulmonary artery (n = 33). The primary outcome measure was the need for operative or catheter-based pulmonary artery intervention. Results No patients in the right ventricle to pulmonary artery group required catheterization-based pulmonary artery interventions. Surgical pulmonary arterioplasty was performed frequently and equally in both the right ventricle to pulmonary artery and right ventricle to pulmonary artery groups at the bidirectional Glenn procedure. Catheter-based pulmonary arterioplasty was performed more frequently in the right ventricle to pulmonary artery conduit group, especially when the conduit was positioned to the right side of the neoaorta. These patients had a 12.73 increased odds of a pulmonary artery intervention compared with the left to right ventricle to pulmonary artery conduit ( P = .04). Conclusions Consistent with a previous multicenter randomized trial, patients who received a right ventricle to pulmonary artery conduit versus a right ventricle to pulmonary artery have a greater risk of requiring pulmonary artery interventions. Patients with right ventricle to pulmonary artery conduit placement to the right underwent a greater number of pulmonary artery interventions but demonstrated overall improved growth of the branch pulmonary arteries compared with the patients receiving a left-sided right ventricle to pulmonary artery conduit.

Abbott RealTime HIV-1 Qualitative is an in vitro real-time PCR assay for detecting HIV-1 nucleic acids in human plasma and dried blood spots (DBS). The assay was designed to be used in diagnosis of HIV-1 infections in pediatric and adult patients, with an emphasis on the applicability in resource-limited settings. Use of DBS facilitates specimen collection from remote areas and transportation to testing laboratories. Small sample input requirement facilitates testing of specimens with limited collection volume. The Abbott RealTime HIV-1 Qualitative assay is capable of detecting HIV-1 group M subtypes A-H, group O and group N samples. HIV-1 virus concentrations detected with 95% probability were 80 copies/mL of plasma using the plasma protocol, and 2469 copies/mL of whole blood using the DBS protocol. The assay detected HIV-1 infection in 13 seroconversion panels an average 10.5 days earlier than an HIV-1 antibody test and 4.9 days earlier than a p24 antigen test. For specimens collected from 6 weeks to 18 months old infants born to HIV-1 positive mothers, assay results using both the DBS and plasma protocols agreed well with the Roche Amplicor HIV-1 DNA Test version 1.5 (95.5% agreement for DBS and 97.8% agreement for plasma).

Background Abbott RealTime High Risk (HR) HPV is a recently developed test for the detection of 14 high-risk oncogenic HPV types combined with the ability to concurrently identify genotypes 16 and 18. Objectives The clinical performance of the Abbott RealTime HR HPV test was evaluated in comparison with the Hybrid Capture 2 (HC2) test for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). The relative accuracy of the Abbott RealTime HR HPV to detect high-risk HPV was also determined. Study design Cervical specimens were collected from 702 patients with abnormal cytology who were referred for colposcopy, and were tested with liquid based cytology (LBC), Abbott RealTime HR HPV and HC2. Genotyping was done using the Linear Array (LA) method. Histological assessment was used as the gold standard for disease status. Clinical performance for detection of disease was evaluated for Abbott RealTime HR HPV in comparison with HC2 in the overall population and in each cytological grade. The relative accuracy for detection of high-risk HPV was assessed by concordance between the two tests and based on LA genotyping. Results and Conclusions The Abbott RealTime HR HPV showed similar clinical performance for detection of CIN2+ when compared with HC2, for both the overall population and those with a cytological grade of atypical squamous cells of undetermined significance (ASC-US). The accuracy for detection of high-risk HPV was significantly higher with Abbott RealTime HR HPV than with HC2.

Background Abbott RealTi m e High Risk (HR) HPV is a new automated, qualitative real-time PCR test for detection of DNA from 14 high-risk human papillomavirus (HPV) types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in cervical specimens. The test can also differentiate between HPV 16, HPV 18 and non-HPV 16/18 types in a single reaction. Objectives: This article describes the principles of assay design and the analytical performance of Abbott RealTi m e HR HPV. Study Design The analytical performance characteristics of Abbott RealTi m e HR HPV were evaluated in terms of its sensitivity for each of the 14 high-risk types included in the test, specificity (cross-reactivity), potential for interference by substances that may be present in cervical specimens, and reproducibility. Results Abbott RealTi m e HR HPV provided sensitive detection of the 14 high-risk HPV types included in the test. It was also highly specific to the HPV types targeted by the test and did not show cross-reactivity with 15 low-risk HPV types tested, or non-specific reactivity with other common microorganisms that may be present in the female anogenital tract. Test results were not impacted by potential interfering substances evaluated in the study. The test generated highly reproducible results in an in-house study and in studies carried out at 13 external evaluation sites. Conclusions Abbott RealTi m e HR HPV demonstrated a robust analytical performance with reproducible and reliable results.

Stone has been used as a building material since the literal Stone Age and it is not going to be an extinct construction material anytime soon. While natural stone is used in all aspects of home construction such as exterior wall claddings, in the early 1960's companies began manufacturing synthetic or fake stones that replicated natural stones. Advancements in technology throughout the years have created more authentic artificial stones that continue to replace natural stones for use as exterior wall claddings. Without being an advocate of the synthetic stone industry, the products they manufacture offer many advantages over natural stone. Lower cost, greater availability, wide variety of colors and styles, lighter weight, quicker installation time, small waste factors due to custom stone pieces such as corners and water tables, and repeatability and reliance for the construction trades installing the products are some advantages to manufactured stone. Regardless of the quality of the product used to skin a building, the quality of any exterior cladding ultimately depends on the quality of installation. This article will attempt to provide the reader with the information needed to ensure their stone veneer and related building components do not suffer failures related to the improper installation and lack of detailing at important locations.

The 5' untranslated regions (UTR) of chloroplast mRNAs often contain regulatory sequences that control RNA stability and/or translation. The petD chloroplast mRNA in Chlamydomonas reinhardtii has three such essential regulatory elements in its 362-nt long 5' UTR. To further analyze these elements, we compared 5' UTR sequences from four Chlamydomonas species (C. reinhardtii, C. incerta, C. moewusii and C. eugametos) and five independent strains of C. reinhardtii. Overall, these petD 5' UTRs have relatively low sequence conservation across these species. In contrast, sequences of the three regulatory elements and their relative positions appear partially conserved. Functionality of the 5' UTRs was tested in C. reinhardtii chloroplasts using beta-glucuronidase reporter genes, and the nearly identical C. incerta petD functioned for mRNA stability and translation in C. reinhardtii chloroplasts while the more divergent C. eugametos petD did not. This identified what may be key features in these elements. We conclude that these petD regulatory elements, and possibly the corresponding trans-acting factors, function via mechanisms highly specific and surprisingly sensitive to minor sequence changes. This provides a new and broader perspective of these important regulatory sequences that affect photosynthesis in these algae.

Introduction. Previous research has demonstrated that nonsteroidal anti-inflammatory agents alter the incidence of colorectal cancer. It has been postulated that the response may be due to the effect of these agents on the activities of the cyclooxygenase (COX) enzymes. The COX enzymes catalyze the conversion of arachidonic acid to biologically active prostanoids. Two forms of COX have been identified. COX-1 is a constitutive enzyme, generally involved in cell functions, while COX-2 is commonly an enzyme which is inducible in response to various stimuli, including mitogens. Recently, specific inhibitors of COX-1 and COX-2 enzymes have been developed. Purpose. The present study was undertaken to determine the effects of specific COX-1 and COX-2 inhibitors on the proliferation and the induction of apoptosis of intestinal epithelial cells. Methods. A continuously proliferating rat small intestinal cell line (IEC-18) and a mouse colon cancer cell line (WB-2054) were utilized for these experiments. The cells were placed in microwells with serum-free or serum-supplemented media. The effects of serum on proliferation were then evaluated in the presence of the COX-1 inhibitor, valerylsalicyclic acid (VSA), the COX-2 inhibitor, SC-58125, or indomethacin. The presence of COX-1 and COX-2 protein was evaluated by Western blotting. Proliferation of intestinal cells was quantitated by incorporation of [ 3 H]thymidine into DNA and cell counting, and apoptosis was determined by evaluating cell attachment. COX activity was evaluated by prostaglandin E 2 production measured by enzyme-linked immunoabsorbent assay (ELISA). Results. Western blotting of IEC-18 and WB-2054 cell protein demonstrated COX-1 enzyme in cells incubated in serum-free media with increased COX-1 expression produced by incubation in media supplemented with 10% serum. COX-2 enzyme was not demonstrated in serum-free media; however, it was present in cells maintained in 10% serum-supplemented media. Spontaneous DNA synthesis was present in both cell lines and serum increased proliferation. In both cell lines [ 3 H]thymidine incorporation stimulated by serum was inhibited by the COX-2 inhibitor SC-58125, but not by the COX-1 inhibitor VSA. Both indomethacin and SC-58125 produced a dose-dependent increase in apoptotic ratios in both cell lines. PGE 2 formation, stimulated by serum, was inhibited by SC-58125, VSA, and indomethacin. Conclusions. A differential effect on intestinal cell mitogenesis was seen with different COX inhibitors. The COX-2 inhibitor, but not the COX-1 inhibitor, significantly inhibited [ 3 H]thymidine incorporation in both cell types, suggesting COX-2 inhibitors may be specific inhibitors of normal epithelial cell proliferation and growth of malignant cells. SC-58125, a selective inhibitor of COX-2, has a potent apoptosis inducing effect. The inhibition of PGE 2 production did not correlate with the inhibition of proliferation, suggesting the two processes are unrelated.