Simulated spinal cerebrospinal fluid leak repair: an educational model with didactic and technical components.

BACKGROUND: In the era of surgical resident work hour restrictions, the traditional apprenticeship model may provide fewer hours for neurosurgical residents to hone technical skills. Spinal dura mater closure or repair is 1 skill that is infrequently encountered, and persistent cerebrospinal fluid leaks are a potential morbidity. OBJECTIVE: To establish an educational curriculum to train residents in spinal dura mater closure with a novel durotomy repair model. METHODS: The Congress of Neurological Surgeons has developed a simulation-based model for durotomy closure with the ongoing efforts of their simulation educational committee. The core curriculum consists of didactic training materials and a technical simulation model of dural repair for the lumbar spine. RESULTS: Didactic pretest scores ranged from 4/11 (36%) to 10/11 (91%). Posttest scores ranged from 8/11 (73%) to 11/11 (100%). Overall, didactic improvements were demonstrated by all participants, with a mean improvement between pre- and posttest scores of 1.17 (18.5%; P = .02). The technical component consisted of 11 durotomy closures by 6 participants, where 4 participants performed multiple durotomies. Mean time to closure of the durotomy ranged from 490 to 546 seconds in the first and second closures, respectively (P = .66), whereby the median leak rate improved from 14 to 7 (P = .34). There were also demonstrative technical improvements by all. CONCLUSION: Simulated spinal dura mater repair appears to be a potentially valuable tool in the education of neurosurgery residents. The combination of a didactic and technical assessment appears to be synergistic in terms of educational development

A Two-Stage Random Forest-Based Pathway Analysis Method

Pathway analysis provides a powerful approach for identifying the joint effect of genes grouped into biologically-based pathways on disease. Pathway analysis is also an attractive approach for a secondary analysis of genome-wide association study (GWAS) data that may still yield new results from these valuable datasets. Most of the current pathway analysis methods focused on testing the cumulative main effects of genes in a pathway. However, for complex diseases, gene-gene interactions are expected to play a critical role in disease etiology. We extended a random forest-based method for pathway analysis by incorporating a two-stage design. We used simulations to verify that the proposed method has the correct type I error rates. We also used simulations to show that the method is more powerful than the original random forest-based pathway approach and the set-based test implemented in PLINK in the presence of gene-gene interactions. Finally, we applied the method to a breast cancer GWAS dataset and a lung cancer GWAS dataset and interesting pathways were identified that have implications for breast and lung cancers

High-quality habitat and facilitation ameliorate competitive effects of prior residents on new settlers

Many species disperse during their lifetime. Two factors that can affect the performance of individuals following dispersal are the presence of conspecifics and intrinsic habitat quality at the settlement site. Detecting the influence of these factors can be difficult for at least two reasons: (1) the outcomes of interactions with conspecifics are often variable including both competition and facilitation, and (2) selection of high quality habitats often leads to positive covariance between habitat quality and density. In this study, I investigate positive and negative effects of resident blue streak cleaner wrasse (Labroides dimidiatus) on the growth and survival of recently settled conspecifics while accounting for habitat quality. Juvenile L. dimidiatus settle near adult conspecifics, but likely have to compete with resident adults for access to food. However, field experiments indicate that settlers have access to more resources at occupied sites, and as a result, grow faster despite evidence for competition with residents. This result is a direct consequence of two factors: (1) resident conspecifics facilitate settlers by attracting client fish, and (2) resident conspecifics are strongly associated with high quality habitat. These results highlight the need to simultaneously consider habitat quality and competitive and facilitative interactions between conspecifics when making inferences about ecological processes from spatial patterns of individual performance

Transnational regulation of temporary agency work compromised partnership between Private Employment Agencies and Global Union Federations

This article critically assesses the potential for the international regulation of temporary agency work (TAW) through building partnership between the Global Union Federations (GUFs) and major Private Employment Agencies (PrEAs). Given the limits of existing national and international regulation of TAW, particularly in developing countries, and the current deadlock in dialogue through the International Labour Organization, the argument of this article is that Transnational Private Labour Regulation (TPLR) offers a unique opportunity to establish a basis for minimum standards for temporary agency workers. This article goes on to propose three potential TPLR frameworks that, although compromised, are transparent, fair and sufficiently elastic to accommodate the distributive and political risks associated with partnership. They also offer important gains, namely increasing the competitive advantage of the PrEAs involved, minimum standards for agency workers and ‘field enlarging’ strategies for the GUFs and their affiliates

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated <it>Plasmodium falciparum </it>malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the <it>in vivo </it>efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam^®, Mephaquin^®, and Mefloquina-AC^®Farma) given in combination with artesunate.</p> <p>Methods</p> <p>Thirty-nine non-pregnant adults with <it>P. falciparum </it>mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.</p> <p>Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data.</p> <p>Results</p> <p>By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (C_max) and interquartile range was 2,820 ng/ml (2,614–3,108) for Lariam, 2,500 ng/ml (2,363–2,713) for Mephaquin, and 2,750 ng/ml (2,550–3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the C_maxof Mephaquin which was significantly different to that of Lariam (<it>p </it>= 0.04).</p> <p>Conclusion</p> <p>All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.</p

The African Cichlid Fish Astatotilapia burtoni Uses Acoustic Communication for Reproduction: Sound Production, Hearing, and Behavioral Significance

Sexual reproduction in all animals depends on effective communication between signalers and receivers. Many fish species, especially the African cichlids, are well known for their bright coloration and the importance of visual signaling during courtship and mate choice, but little is known about what role acoustic communication plays during mating and how it contributes to sexual selection in this phenotypically diverse group of vertebrates. Here we examined acoustic communication during reproduction in the social cichlid fish, Astatotilapia burtoni. We characterized the sounds and associated behaviors produced by dominant males during courtship, tested for differences in hearing ability associated with female reproductive state and male social status, and then tested the hypothesis that female mate preference is influenced by male sound production. We show that dominant males produce intentional courtship sounds in close proximity to females, and that sounds are spectrally similar to their hearing abilities. Females were 2–5-fold more sensitive to low frequency sounds in the spectral range of male courtship sounds when they were sexually-receptive compared to during the mouthbrooding parental phase. Hearing thresholds were also negatively correlated with circulating sex-steroid levels in females but positively correlated in males, suggesting a potential role for steroids in reproductive-state auditory plasticity. Behavioral experiments showed that receptive females preferred to affiliate with males that were associated with playback of courtship sounds compared to noise controls, indicating that acoustic information is likely important for female mate choice. These data show for the first time in a Tanganyikan cichlid that acoustic communication is important during reproduction as part of a multimodal signaling repertoire, and that perception of auditory information changes depending on the animal's internal physiological state. Our results highlight the importance of examining non-visual sensory modalities as potential substrates for sexual selection contributing to the incredible phenotypic diversity of African cichlid fishes

A Blueprint for Real-Time Functional Mapping via Human Intracranial Recordings

International audienceBACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz), can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

The Gag Cleavage Product, p12, is a Functional Constituent of the Murine Leukemia Virus Pre-Integration Complex

The p12 protein is a cleavage product of the Gag precursor of the murine leukemia virus (MLV). Specific mutations in p12 have been described that affect early stages of infection, rendering the virus replication-defective. Such mutants showed normal generation of genomic DNA but no formation of circular forms, which are markers of nuclear entry by the viral DNA. This suggested that p12 may function in early stages of infection but the precise mechanism of p12 action is not known. To address the function and follow the intracellular localization of the wt p12 protein, we generated tagged p12 proteins in the context of a replication-competent virus, which allowed for the detection of p12 at early stages of infection by immunofluorescence. p12 was found to be distributed to discrete puncta, indicative of macromolecular complexes. These complexes were localized to the cytoplasm early after infection, and thereafter accumulated adjacent to mitotic chromosomes. This chromosomal accumulation was impaired for p12 proteins with a mutation that rendered the virus integration-defective. Immunofluorescence demonstrated that intracellular p12 complexes co-localized with capsid, a known constituent of the MLV pre-integration complex (PIC), and immunofluorescence combined with fluorescent in situ hybridization (FISH) revealed co-localization of the p12 proteins with the incoming reverse transcribed viral DNA. Interactions of p12 with the capsid and with the viral DNA were also demonstrated by co-immunoprecipitation. These results imply that p12 proteins are components of the MLV PIC. Furthermore, a large excess of wt PICs did not rescue the defect in integration of PICs derived from mutant p12 particles, demonstrating that p12 exerts its function as part of this complex. Altogether, these results imply that p12 proteins are constituent of the MLV PIC and function in directing the PIC from the cytoplasm towards integration