Barriers in precision medicine implementation among Advanced Nonsquamous Cell Lung Cancer-patients: A Real-World Evidence Scenario.

Background: Precision oncology has a prominent role in nonsquamous non-small cell lung cancer (nsNSCLC) treatment progress; however, its access in a real-world scenario might be limited. Objective: To investigate the time spent in nsNSCLC molecular profile evaluation and its influence on clinical decisions. Methods: nsNSCLC patients who underwent molecular testing in a private referral Brazilian center between November 2015 and February 2020 were identified. The interval from nsNSCLC diagnosis to the characterization of the molecular profile was determined. Other outcomes, focusing on the biomarker tissue journey, were also assessed. Results: In this cohort (n = 78), the median time between the advanced nsNSCLC diagnosis and biomarker characterization was 40.5 days (range, 29.5-68.5). The median interval between the diagnosis and the test request was longer than the interval between the request and the results (respectively 29.0 versus 12.0 days; p < 0.001). At the treatment initiation, 51% (36/71) of the patients who received any systemic therapy did not have their driver mutations panel results available. But on these, 42% (15/36) had a targetable alteration identified later on. Among patients harboring a targetable alteration, only 46% (n = 13/28) received a tyrosine kinase inhibitor (TKI) as first-line therapy. The median time to the TKI initiation was even longer than the median time to all treatment initiation (92.0 versus 40.0 days). Conclusions: Our data show a long median time from advanced nsNSCLC diagnosis and the availability of the biomarker testing in medical practice, which impacted the choice of a non-personalized therapy as the first-line.

Impact of tranexamic acid use on blood loss and transfusion rates following femoral varus derotational osteotomy in children with cerebral palsy.

PURPOSE: Previous studies have established the safety and efficacy of tranexamic acid (TXA) in reducing blood loss after total joint arthroplasty and spinal fusion surgery; however, literature regarding the effectiveness of intraoperative TXA in children with cerebral palsy (CP) is limited. The aim of this study was to investigate the safety and efficacy of intraoperative TXA in reducing blood loss and transfusion requirements for children with CP undergoing a proximal femoral varus derotational osteotomy (VDRO). METHODS: This is a retrospective review of 258 children with CP who underwent VDRO performed at the author's institution between 2004 and 2017. In all, 36 subjects underwent VDRO surgery with administration of intravenous TXA and 222 subjects underwent VDRO without administration of TXA. Outcome measures including blood loss, transfusion requirements and venous thromboembolic events were compared between groups using t-tests and chi-squared tests. RESULTS: No significant differences were seen in the rates of transfusion between groups for the entire hospitalization (TXA group: 11.1% versus No TXA group: 19.8%), intraoperatively (TXA: 2.8% versus No TXA: 9.0%) or postoperatively (TXA: 8.3% versus No TXA: 14.4%). Intraoperative estimated blood loss (TXA: 144.4 mL versus No TXA: 159.0 mL) and percentage blood loss (TXA: 8.9% versus No TXA: 9.2%) were similar between groups. No major thromboembolic complications events occurred in either group. CONCLUSION: The use of TXA was not associated with thromboembolic complications in this series of children with CP undergoing VDRO surgery. Though there was a trend toward lower rates of intraoperative and postoperative blood transfusion with TXA use in these patients, the differences were not significant, possibly due to low estimated blood loss in both groups and sample size. LEVEL OF EVIDENCE: III- retrospective comparative study.

Integrated coastal management of Dakshina Kannada and Udupi--a case study.

A concerted effort is needed to achieve sustainable and equitable development of the coastal regions of India. In this direction government of India has initiated the processes of putting in place integrated coastal management through the Department of Ocean Development. The study area, an ecologically sensitive region is developing at a very fast rate, however, the development has neither been uniform nor spread over the entire region, rather it has been concentrated in Dakshina Kannada district alone. Innovative technologies have been introduced in the area of capture and culture fisheries and also there has been major industrial development. These two aspects have led to user-user conflict and concern for environmental degradation. The study reveals an urgent need to put in place processes leading to integrated coastal management. Cause and effects have been discussed and possible remedies suggested.

Central and peripheral components of short latency vestibular responses in the chicken.

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Electrophore-labeling and alkylation of standards of nucleic acid pyrimidine bases for analysis by gas chromatography with electron-capture detection.

The pyrimidine bases cytosine, uracil and thymine, along with some analogues, are electrophore-labeled either with pentafluorobenzoyl chloride (PFBC), pentafluorophenylsulfonyl chloride (PPSC), or heptafluorobutyric anhydride. Subsequent alkylation is most successful for PFB-cytosine, PPS-uracil, and PPS-thymine. These same alkylated compounds also have the highest aqueous stability and respond most strongly by gas chromatography-electron-capture detection. One of these derivatives, determined to be N4-PFB-1,3-dimethylcytosine by authentic synthesis, and its 5-methyl analogue, can be detected with good precision down to the 100-fg level. Poor reproducibility is encountered at the 10-fg level.

Gas chromatography-mass spectrometry characteristics of methylated perfluoroacyl derivatives of cytosine and 5-methylcytosine.

Pentafluorobenzoyl and heptafluorobutyryl derivatives of cytosine and pentafluorobenzoyl-5-methylcytosine have been examined by mass spectrometry following permethylation. Electron impact mass spectra were used to confirm the structures of the derivatives. The permethylated pentafluorobenzoyl derivatives of cytosine and 5-methylcytosine are sensitive for quantitative analysis by capillary gas chromatography-mass spectrometry. Under negative ion chemical ionization conditions 1 femtogram of each is detected.

Evidence for surface effects in an electron-capture detector.

We have found surface effects in a conventional electron-capture detector that are significantly reduced in an experimental, more inert version of this detector, both by Varian. These surface effects generate unique patterns of solute response for both pesticides-herbicides, and derivatized cytosine strong electrophores. They also cause a minimum followed by a more pronounced maximum in the response factor with increasing solute concentration, demonstrated with lindane. Certain speculations are presented to account for these observations.

Automated analysis of antiepileptic drugs in serum by column-switching high-performance liquid chromatography.

An automated high-performance liquid chromatographic column-switching system is presented for the analysis of antiepileptic drugs in serum. Initial results show that a reversed-phase extraction column works best overall when fitted with screens versus frits, and when packed with porous 30-micron particles as opposed to a pellicular packing of similar size or with smaller porous particles. The continuous analysis of primidone for over 2000 serum samples is achieved at a rate of twelve samples per hour with a single analytical column. An analogous boxcar high-performance liquid chromatographic system is also assembled and used to analyze two of four injected antiepileptic drugs at a rate of 40 samples per hour. For 1000 of these analyses, the coefficient of variation is 1% without an internal standard.