Nevin Manimala Statistics

Analysis of cycle threshold values in SARS-CoV-2-PCR in a long-term study

J Clin Virol. 2021 Mar 10;138:104791. doi: 10.1016/j.jcv.2021.104791. Online ahead of print.


BACKGROUND: Cycle threshold (Ct) values can be used in an attempt to semiquantify results in the qualitative real-time polymerase-chain-reaction (PCR) for the new coronavirus SARS-CoV-2. The significance of Ct values in epidemiological studies and large cohorts is still unclear.

OBJECTIVE: To monitor Ct values in a long-term study and compare the results with demographic data of patients who tested positive for SARS-CoV-2 by real-time PCR.

STUDY DESIGN: S gene SARS-CoV-2 Ct values were analyzed retrospectively from consecutive patients between March 15th to September 15th 2020 with special regard to age, gender, and in- or outpatient status.

RESULTS: In total, 65,878 patients were tested, 1103 (1.7 %) of whom were positive for SARS-CoV-2. Twenty-six positive patients were excluded, because the respective PCR runs did not meet the stability requirements (Ct value of the positive controls between 26 and 29). Of the remaining 1077 patients, females (n = 566; 53 %) were significantly older than males (n = 511; 47 %) (50.9 versus 45.1 years; p = 0.006) and had slightly higher mean Ct values than males (25.4 vs. 24.8; p = 0.04). Patients in the age groups >80 years had significantly higher Ct values than the remaining age groups (p < 0.001). Children (0-19 years) showed Ct values in the range of those found in adults (25.2 vs. 25.1, p = 0.9). There were no statistically different Ct values between in- and outpatients (p = 0.1), however, SARS-CoV-2 positive inpatients were significantly older than outpatients (p < 0.0001).

CONCLUSIONS: CT values are suitable for more detailed monitoring of the SARS-CoV-2 pandemic. Age is an important cofactor in SARS-CoV-2 positive patients and may have influence on Ct values in SARS-CoV-2-PCR.

PMID:33725648 | DOI:10.1016/j.jcv.2021.104791

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An exploration on the form factors of turbulence kinetic energy transfer for shear exfoliation of graphene

Nanotechnology. 2021 Mar 16. doi: 10.1088/1361-6528/abef2d. Online ahead of print.


Producing defect-free and large-lateral-size 2D materials via cost-effective methods is important for mass application. Recently, shear exfoliation showed great promise for large-scale production due to its simple operation, environmental-benignity, and wide adaptability. However, a long-standing challenge is that with more nanosheets produced, a ceiling yield and shattered products are encountered, which significantly limit their wider application. The way and efficiency of energy transfer in fluid is undoubtedly the key point in determining the exfoliation efficiency, yet there has no in-deep mechanism elucidation so far. Thus, a thorough investigation regarding the turbulence energy transfer is critically necessary. Herein, we identify two main factors which critically determine the exfoliation yield and provide a statistical analysis on the relationship between these factors and exfoliation yield. In the initial shearing process, the coexistence of the 2D nanosheets and raw particles is the dominant factor; with time passes by, the dimensional change of raw materials gradually shows more influence on the energy transfer. These factors together lead to attenuated efficiency and a power function relationship between yield and exfoliation time. This investigation gives a statistical explanation regarding shear exfoliation technology for 2D materials preparation and provides valuable insights for mechanical exfoliating high-quality 2D materials.

PMID:33725678 | DOI:10.1088/1361-6528/abef2d

Nevin Manimala Statistics

Rising Global Opportunities Among Orthopaedic Surgery Residency Programs

J Am Acad Orthop Surg Glob Res Rev. 2020 Dec 14;4(12):e20.00102. doi: 10.5435/JAAOSGlobal-D-20-00102.


OBJECTIVE: We surveyed Orthopaedic Surgery Residency (OSR) programs to determine international opportunities by the academic institutional region within the United States, location of the international experience, duration, residency program year (PGY), funding source, and resident participation to date.

DESIGN: We emailed a survey to all OSR programs in the United States to inquire about global opportunities in their residency programs. Further contact was made through an additional e-mail and up to three telephone calls. Data were analyzed using descriptive and chi-square statistics. This study was institutional review board exempt.

SETTING: This research study was conducted at the University of Nebraska Medical Center, a tertiary care facility in conjunction with the University of Nebraska Medical Center College of Medicine.

PARTICIPANTS: The participants of this research study included program directors and coordinators of all OSR programs (185) across the United States.

RESULTS: A total of 102 OSR programs completed the survey (55% response rate). Notably, 50% of the responding programs offered a global health opportunity to their residents. Of the institutions that responded, those in the Midwest or South were more likely to offer the opportunity than institutions found in other US regions, although regional differences were not significant. Global experiences were most commonly: in Central or South America (41%); 1 to 2 weeks in duration (54%); and during PGY4 or PGY5 (71%). Furthermore, half of the programs provided full funding for the residents to participate in the global experience. In 33% of the programs, 10 or more residents had participated to date.

CONCLUSIONS: Interest in global health among medical students is increasing. OSR programs have followed this trend, increasing their global health opportunities by 92% since 2015. Communicating the availability of and support for international opportunities to future residents may help interested students make informed decisions when applying to residency programs.

PMID:33725703 | DOI:10.5435/JAAOSGlobal-D-20-00102

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The impact of symptomatic femoral neck anteversion and tibial torsion on gait, function and participation in children and adolescents

Gait Posture. 2021 Mar 8;86:144-149. doi: 10.1016/j.gaitpost.2021.03.004. Online ahead of print.


BACKGROUND: Torsional deformities of the lower limbs in children and adolescents are a common cause of in-toeing gait and cause gait deviations. The purpose of this study was to examine the relationship of children and adolescents with suspected Idiopathic Torsional Deformities (ITD) and pain, gait function, activity and participation.

METHODS: A retrospective review of all children and adolescents who attended our Centre over a 5-year period for evaluation of the effect of ITD. All children completed three-dimensional gait analysis (3DGA), standardized physical examination, medical imaging and the Pediatric Outcomes Data Collection Instrument (PODCI). Statistical analysis was completed using two sample t-tests, Pearson’s Correlation and linear regression.

RESULTS: Fifty children and adolescents, 40 females and 10 males with a mean age of 13.5 years were included. Children reported a high prevalence of pain(86%), had increased internal hip rotation(p = 0.002) and decreased external hip rotation(p < 0.001) on physical examination when compared to published normative data. Medical imaging showed a mean(SD) femoral neck anteversion (FNA) of 38°(13°) and external tibial torsion of 39°(12°). Mean(SD) PODCI score was 32(16), indicating these children are functioning below their typically developing peers. The 3DGA kinematics show deviations from typical data including hip rotation, foot progression, pelvic tilt, hip flexion and knee extension. Observed mild kinetic deviations were within typical limits. The relationship between FNA and gait parameters, FNA and PODCI and gait and PODCI were weak.

SIGNIFICANCE: These children and adolescents have altered gait and experience pain leading to impaired function and diminished participation. Therefore, ITD is not purely a cosmetic issue.

PMID:33725582 | DOI:10.1016/j.gaitpost.2021.03.004

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Effect of different forefoot rocker radii on lower-limb joint biomechanics in healthy individuals

Gait Posture. 2021 Mar 6;86:150-156. doi: 10.1016/j.gaitpost.2021.03.008. Online ahead of print.


INTRODUCTION: Previous studies showed that rocker shoes with a stiff forefoot rocker profile significantly reduce peak plantar flexion moment at the ankle (PFM) and peak ankle dorsiflexion (DF). Both parameters are related to Achilles tendon and Plantar Fascia unloading. The shape of an outsole with a forefoot rocker is described with multiple rocker design parameters. The aim of this research is, to determine the relation between different forefoot rocker radii on peak DF and peak PFM at a self-selected walking speed.

METHODS: 10 participants walked in standard shoes and three experimental pairs of shoes with different forefoot rocker radii. Lower extremity kinematics and kinetics were collected while walking on an instrumented treadmill at preferred walking speed and analysed with Statistical Parametric Mapping (SPM) (α = .05; post-hoc α = .05/6).

RESULTS: Peak value analyses showed significant decreases in peak DF, peak PFM, and peak ankle power generation for the rocker conditions. No relevant significant differences were found in spatio-temporal parameters and total work at the ankle joint. SPM showed a significant decrease (% gait cycle) in DF (40-69 %), PFM (7-15 %; 41-68 %; 69-81 %), ankle power (10-15 %; 32-51 %; 55-64 %; 64-67 %; 72-80 %) and foot-to-horizontal angle (FHA) (0-4 %; 40-62 %; 92-100 %) and an increased shank-to-vertical angle (SVA) (44-84 %) for the rocker conditions.

CONCLUSION: The results of this study suggest that rocker shoes with a proximally placed apex significantly reduce DF and PFM during the third rocker compared with control shoes. This effect is mainly explained by a change in the FHA. Smaller radii cause the largest reductions in DF and PFM, so therefore, a uniform standardisation of the forefoot rocker radius is essential.

PMID:33725583 | DOI:10.1016/j.gaitpost.2021.03.008

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Altered tonsillar toll-like receptor (TLR)-1 and TLR-2 expression levels between periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), and group A beta-hemolytic streptococcal (GAβHS) recurrent tonsillitis patients

Int J Pediatr Otorhinolaryngol. 2021 Mar 10;144:110674. doi: 10.1016/j.ijporl.2021.110674. Online ahead of print.


INTRODUCTION: Tonsillar microenvironment is thought to contribute to innate immune dysregulation responsible for the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) because of beneficial effects of tonsillectomy on treatment of the syndrome. Accordingly previous studies reported altered lymphocyte frequency, cytokine level and microbial composition in PFAPA tonsils. The aim of our study is to monitor expression levels of pro-inflammatory cell surface Toll-like receptors (TLRs) which have important role in induction of inflammation and maintaining tissue haemostasis.

MATERIALS AND METHODS: Seven patients with PFAPA syndrome, and eight patients with group A beta-hemolytic streptococcal (GAβHS) recurrent tonsillitis were included in our study. Tonsillar expression levels of TLR-1, -2, -4, -5, and -6 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test.

RESULTS: IHC analysis demonstrated expression of all TLRs in tonsillar surface epithelium (SE) and lymphoid interior (LI) except for TLR-6 which was not present in the former. There has not been any statistically significant difference in TLR expression levels between PFAPA and GAβHS tonsils, except for TLR-1 and TLR-2 which were higher on LI and lower on SE of PFAPA tonsils, respectively, than that of the GAβHS samples.

CONCLUSIONS: Altered TLR expression levels may be involved in PFAPA pathogenesis. Future studies with higher patient number, uninflamed tonsils and cellular markers are required to further enlighten the role of TLRs in the development of syndrome.

PMID:33725589 | DOI:10.1016/j.ijporl.2021.110674

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All HPV-negative head and neck cancers are not the same: Analysis of the TCGA dataset reveals that anatomical sites have distinct mutation, transcriptome, hypoxia, and tumor microenvironment profiles

Oral Oncol. 2021 Mar 13;116:105260. doi: 10.1016/j.oraloncology.2021.105260. Online ahead of print.


PURPOSE: Head and neck squamous cell carcinoma (HNSCC) affects various anatomical sites, which often dictates whether the cancer is managed with primary surgery or radiation. This study aimed to assess differences in single nucleotide variation (SNV), copy number, mRNA abundance, methylation, and tumor microenvironment (TME) between HPV-negative oral cavity (OC), oropharyngeal (OPC), hypopharyngeal (HPC), and laryngeal (LC) cancers within The Cancer Genome Atlas (TCGA).

METHODS: We downloaded the clinical information and molecular data for the TCGA HNSCC cohort from the data portal and published literature. The TME was estimated using mRNA abundance data. We conducted our analyses within the Bioconductor statistical framework in the R environment. CNA and mRNA abundance results were correlated and grouped with SNV results for downstream pathway analysis.

RESULTS: LC had a higher mutational burden than OC and OPC (p <10-4). LC tumors were enriched in CSMD3, NSD1, DCHS2 and ANK2 SNVs, while OC tumors were enriched in CASP8 SNVs (FDR < 0.1). LCs were enriched for neuronal and glycosylation pathways, while OCs were enriched for extracellular matrix pathways. B cells and endothelial cells were more abundant in LC while monocytes were more abundant in OC (FDR < 0.1). OPC was the most hypoxic, followed by OC then LC (FDR < 0.05). OC had greater methylation of Hox genes than LC. Subsite analysis revealed that oral tongue cancers had fewer CASP8 and FBN2 mutations and higher dendritic cell abundance than other oral cavity cancers.

CONCLUSIONS: We identified significant genomic, transcriptional, and microenvironmental differences between HPV-negative HNSCC. Further study is warranted to determine if these findings portend differential response to specific treatment modalities.

PMID:33725617 | DOI:10.1016/j.oraloncology.2021.105260

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Brief High Oxygen Concentration Induces Oxidative Stress in Leukocytes and Platelets – A Randomised Cross-Over Pilot Study in Healthy Male Volunteers

Shock. 2021 Jan 20. doi: 10.1097/SHK.0000000000001728. Online ahead of print.


BACKGROUND: Supplemental oxygen is administered routinely in the clinical setting to relieve or prevent tissue hypoxia, but excessive exposure may induce oxidative damage or disrupt essential homeostatic functions. It is speculated that oxidative stress in leukocytes and platelets may contribute to vascular diseases by promoting inflammation and cell aggregation.

METHODS: In this pilot study thirty healthy male volunteers (18 to 65 years) were exposed to high oxygen concentration (non-rebreather mask, 8L/min, 100% O2) and synthetic air (non-rebreather mask, 8L/min, 21% O2) in a cross-over design for 20 min at a 3-week interval. Venous blood samples were obtained at baseline and 1, 3 and 6 h post-intervention. Primary outcome was generation of reactive oxygen species in leukocytes as measured by the redox-sensitive fluorescent dye dihydrorhodamine 123. Additional outcomes were oxidative stress in platelets and platelet aggregation as measured by thromboelastography (ROTEM®) and Multiplate analyses.

FINDINGS: High oxygen exposure induced oxidative stress in leukocytes as evidenced by significantly higher mean fluorescence intensity (MFI) compared with synthetic air at 3 hours post-intervention (47% higher, P = 0.015) and 6 h post-intervention (37% higher, P = 0.133). Oxidative stress was also detectable in platelets (33% higher MFI in comparison with synthetic air at 6 h, P = 0.024; MFI 20% above baseline at 3 h, P = 0.036; 37% above baseline at 6 h, P = 0.002). ROTEM® analyses demonstrated reduced mean clotting time 1 h post-intervention compared with baseline (-4%, P = 0.049), whereas there were no significant effects on other surrogate coagulation parameters.

CONCLUSION: Clinically relevant oxygen exposure induces oxidative stress in leukocytes and platelets, which may influence the immune and clotting functions of these cells.

PMID:33725433 | DOI:10.1097/SHK.0000000000001728

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Intra-operative fluorescein videoangiography-related nephrotoxicity in intracranial aneurysm surgery: Single center, observational cohort study

Clin Neurol Neurosurg. 2021 Mar 11;203:106597. doi: 10.1016/j.clineuro.2021.106597. Online ahead of print.


OBJECTIVES: Intra-operative fluorescein video angiography (FL-VA) has been given increasing attention recently and several studies reported its high utility in neurovascular surgery. The aim of this study was to evaluate the safety of FL-VA in a prospective, single-center cohort of patients operated due to cerebral aneurysms.

PATIENTS AND METHODS: This is an observational cohort study including 150 patients operated due to intracranial aneurysms. The study group consisted of 70 consecutive patients operated with the use of fluorescein video angiography. Post-operative acute kidney injury (AKI) occurrence as well as systemic adverse reactions were reported and further compared with 80 matched controls where FL-VA was not used. Statistical analysis was performed using non-parametric tests (Fisher’s exact test).

RESULTS: Post-operative AKI was observed in 17,1% of patients in the study group with only half presenting with acute functional impairment. All of these patients presented initially due to aneurysm rupture. Pre-existing renal dysfunction and hypertension occurred in 16,7% and 33,3%, respectively. No systemic complications following FL-VA were reported. When compared to matched controls, no statistically significant difference regarding AKI occurrence was observed between these two patient populations.

CONCLUSION: Intra-operative fluorescein video angiography proved to have a good safety profile in our cohort. The results of this study suggest that post-operative acute kidney injury observed in patients with subarachnoid hemorrhage is not related to fluorescein use.

PMID:33725507 | DOI:10.1016/j.clineuro.2021.106597

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Spike wave characteristics and temporal spike evolution on serial EEG in childhood epilepsy with centrotemporal spikes

Seizure. 2021 Mar 3;87:75-80. doi: 10.1016/j.seizure.2021.02.032. Online ahead of print.


PURPOSE: To assess the spike characteristics and temporal spike evolution on serial EEG of children with childhood epilepsy with centrotemporal spikes (CECTS) treated with anti-seizure medication.

METHODS: The study cohort consisted of 127 children with CECTS divided into three groups based on anti-seizure medication responsiveness: group I: seizure-free with monotherapy (n: 61, 48%), group II: seizure-controlled with monotherapy (n: 52, 41%) and group III: seizure-controlled with dual therapy (n: 14, 11%). The clinical profiles and sequential four-year follow-up visual EEG recordings of the children were evaluated. Each EEG was reanalyzed with three spike characteristics on the epochs: (1) spike-wave rate, (2) spike topography, and (3) spike localization. We calculated the spike clearance velocity, which is defined as a decrease in the spike-wave rate over time in four-year sequential follow-up EEGs.

RESULTS: There was no statistical significance across the study groups with respect to initial EEG spike characteristics (spike-wave rate, spike localization, and spike topography). Seizure recurrence occurred in 15 patients (12.8%) who discontinued anti-seizure medication. There was no statistically significant difference between the spike characteristics on EEG just before the discontinuation of anti-seizure medication and seizure recurrence. However, the spike clearance velocity was significantly slower in group III than in group I in four-year sequential follow-up EEGs (p = 0.002). A statistically significant decrease in the mean spike-wave rate was observed in group I in the first year of anti-seizure medication (p<0.001). The spike clearance velocity was also more prominent during the second year of treatment in group II and the third year of treatment in group III. However, the spike clearance velocity was not different across the anti-seizure medication groups (oxcarbazepine, valproic acid, and levetiracetam).

CONCLUSION: Spike clearance velocity might be a valuable EEG marker to guide anti-seizure medication in children with CECTS.

PMID:33725524 | DOI:10.1016/j.seizure.2021.02.032