Immunohistochemical expression of p16INK4a in premalignant lesions and malignant tumours of cervix

Background: Cervical carcinoma is the third most common cancer in women worldwide and firth most common cause of cancer related deaths. Human Papilloma virus, the most common cause of cervical cancer, causes functional inactivation of pRb, resulting in overexpression of p16INK4a. The overexpression of p16INK4a correlates well with the degree of cervical dysplasia and neoplasia. The present study is done to determine the IHC expression of p16INK4a so that it may be used as a biomarker for HPV and may play a role in the prevention, diagnosis and prognosis of cervical neoplasm. Methods: The present study was conducted on 60 formalin-fixed, paraffin-embedded specimens of cervical neoplasms, which comprised 47 cases of squamous cell carcinoma followed by 8 cases of adenocarcinoma, 3 cases of HSIL and 2 cases of LSIL. These were then subjected to IHC by p16INK4a. Cytoplasmic and nuclear positivity for p16INK4a was noted. Results: Overall 95% cases were positive for p16INK4a expression, 100% cases of adenocarcinoma, 98% cases of squamous cell carcinoma, 100% cases of HSIL and 0% cases of LSIL were positive for p16 expression. Conclusions: The present study showed statistical correlation of immunoreactivity of p16INK4a with histological type was clinically significant (p value <0.0001). In our study, p16INK4a immunohistochemical expression increased with increasing degree of dysplasia and with presence of cervical carcinoma

Variations of Field Line Eigenfrequencies With Ring Current Intensity

We present results from the closed magnetosphere (5.9≤L < 9.5 over all magnetic local times) to demonstrate and assess the variations in field line eigenfrequency with geomagnetic activity. Using the time-of-flight technique with realistic magnetic field and mass density models, the spatial distributions of field line eigenfrequencies are determined for a range of different geomagnetic activity levels, as defined by the Dst index. The results indicate that during geomagnetically active conditions, the eigenfrequency of a given field line is generally decreased compared to quiet times, in addition to variations in local asymmetries. By comparing the dependence to changes in the magnetic field and mass density distribution, it is established that the inflation and weakening of the geomagnetic field outweighs decreased plasma mass density and is the sole contributor to decreased eigenfrequencies with increased geomagnetic activity. We highlight the importance of considering the magnetic field, mass density, and average ion mass contributions when using observed eigenfrequencies to probe magnetospheric conditions. Furthermore, the estimates significantly improve upon existing time-of-flight results, through a consideration of mass density changes with geomagnetic activity. We also provide estimates of eigenfrequencies for a comparatively extended spatial region than available from prior direct observations of field line resonances. The results have clear implications for furthering our understanding of how wave energy propagates throughout the magnetosphere during geomagnetic storms

Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT

The Changing Eigenfrequency Continuum during Geomagnetic Storms:Implications for Plasma Mass Dynamics and ULF Wave Coupling

Geomagnetic storms are one of the most energetic space weather phenomena. Previous studies have shown that the eigenfrequencies of ultralow frequency (ULF) waves on closed magnetic field lines in the inner magnetosphere decrease during storm times. This change suggests either a reduction in the magnetic field strength and/or an increase in its plasma mass density distribution. We investigate the changes in local eigenfrequencies by applying a superposed multiple‐epoch analysis to cross‐phase spectra from 132 geomagnetic storms. Six ground magnetometer pairs are used to investigate variations from approximately 3 4, the eigenfrequencies decrease by as much as 50% relative to their quiet time values. Both a decrease in magnetic field strength and an increase in plasma mass density, in some locations by more than a factor of 2, are responsible for this reduction. The enhancement of the ring current and an increase in oxygen ion density could explain these observations. At L < 4, the eigenfrequencies increase due to the decrease in plasma mass density caused by plasmaspheric erosion

Capturing uncertainty in magnetospheric ultra-low frequency wave models

We develop and test an empirical model predicting ground-based observations of ultra-low frequency (ULF, 1-20 mHz) wave power across a range of frequencies, latitudes and magnetic local time sectors. This is parameterized by instantaneous solar wind speed $v_{sw}$, variance in proton number density $var(Np)$ and interplanetary southward magnetic field $B_z$. A probabilistic model of ULF wave power will allow us to address uncertainty in radial diffusion coefficients and therefore improve diffusion modeling of radial transport in Earth's outer radiation belt. Our model can be used in two ways to reproduce wave power; by sampling from conditional probability distribution functions or by using the mean (expectation) values. We derive a method for testing the quality of the parameterization and test the ability of the model to reproduce ULF wave power time series. Sampling is a better method for reproducing power over an extended time period as it retains the same overall distribution while mean values are better for predicting the power in a time series. The model predicts each hour in a time series better than the assumption that power persists from the preceding hour. Finally, we review other sources of diffusion coefficient uncertainty. Although this wave model is designed principally for the goal of improved radial diffusion coefficients to include in outer radiation belt diffusion based modeling, we anticipate that our model can also be used to investigate the occurrence of ULF waves throughout the magnetosphere and hence the physics of ULF wave generation and propagation

A study of the prevalence of various lower urinary tract symptoms in children with analysis of comorbidities and uroflowmetry

Background: The International Children’s Continence Society (ICCS) in its standardization article in 2006 and subsequent revision in 2014 have provided guidelines for the diagnosis and management of lower urinary tract symptoms (LUTS) in children. However, the terminologies are still not in common parlance and colloquial terms are being heavily used in India. Objective: The objective of the study was to evaluate the clinical spectrum of LUTS and their comorbidities in children. Materials and Methods: This was an observational cross-sectional study conducted in a tertiary care hospital in Northern India. Children, included in the study, aged 5–12 years who presented with LUTS as defined in the ICCS 2014 updated guidelines. A simultaneous analysis of uroflowmetry graphs was also done in these children and the observations presented in this paper. Results: Enuresis was the most common LUTS with which children presented to the OPD (78% cases) followed by increased frequency of micturition (42%). Among comorbidities, constipation was present in one-third patients of LUTS. Uroflowmetry done in LUTS often yields a normal “bell-shaped” graph in majority of the patients (71%). The study shows that many enuretics have underlying other LUTS and comorbidities that we should be aware of and uroflowmetry, if not coupled with urodynamic studies, is not a game changer. Conclusion: There are not many studies post the standardization of the ICCS conducted in India and this study aims at increasing the awareness of the same among physicians and researchers alike

Supraclavicularis proprius muscle associated with supraclavicular nerve entrapment

Entrapment neuropathy of the supraclavicular nerve is rare and, when it occurs, is usually attributable to branching of the nerve into narrow bony clavicular canals. We describe another mechanism for entrapment of this nerve with the aberrant muscle; supraclavicularis being found during the routine dissection of an embalmed 82-year-old cadaver. Our report details a unique location for this rare muscular variation whereby the muscle fibres originated posteriorly on the medial aspect of the clavicle before forming a muscular arch over the supraclavicular nerve and passing laterally towards the trapezius and acromion. We recommend that in clinical instances of otherwise unexplained unilateral clavicular pain or tenderness, nerve compression from the supraclavicularis muscle must be borne in mind.