An inventory-location optimization model for equitable influenza vaccine distribution in developing countries during the COVID-19 pandemic

The addition of other respiratory illnesses such as flu could cripple the healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. An annual seasonal influenza vaccine is the best way to help protect against flu. Fears of coronavirus have intensified the shortage of influenza shots in developing countries that hope to vaccinate many populations to reduce stress on their health services. We present an inventory-location mixed-integer linear programming model for equitable influenza vaccine distribution in developing countries during the pandemic. The proposed model utilizes an equitable objective function to distribute vaccines to critical healthcare providers and first responders, elderly, pregnant women, and those with underlying health conditions. We present a case study in a developing country to exhibit efficacy and demonstrate the optimization model’s applicability.     

Congenital lens coloboma and associated pathologies

Coloboma of the lens is characterized by notching of the equator of the lens. The cause of the condition is faulty development of the zonule. The lens deprived of its normal pull in the defective region is thicker and more spherical as if there were no loss of its substance. We report five cases of lens coloboma and localized zonular defect without any associated systemic anomalies. One case included retinal detachment; another included an iris coloboma; and a third included iris, choroid and optic disk colobomas and retinal detachment with lens coloboma. The remaining two cases were without associated ocular anomalies. The pathogenic mechanisms and relationship of this defect with the differentiation of the tertiary vitreous and development of the zonule is discussed. The defect most likely occurs in the third to fourth months of gestation during differentiation of the tertiary vitreous in response to toxic, inflammatory or genetic factors.     

Urethro-vesical function during spinal shock

Summary Twenty spinal shock patients were investigated with simultaneous urethrovesical, anal and rectal pressure recordings and EMG of the external urethral and anal sphincters. Dynamic and static urethral pressure profiles (UPP) were carried out with empty and full bladder. Baldder filling was accompanied by an increased resistance in the internal sphincter zone, which in turn was paralleled in the majority of cases by an elevation of pressure in the membranous urethra without concomitant increase of its EMG activity. This is suggestive of an increased sympathetic activity in the bladder neck area and in the smooth muscle component of the external urethral sphincter. Dynamic pullthrough UPP's displayed higher resistances in the membranous urethra than static interrupted UPP's pointing to the role played by the urethral muscosal receptors in eliciting artefactual results. Higher pressures were recorded in the juxtabulbar portion of the membranous urethra than in its mid portion pointing to a gradient of pressure within the external urethral sphincter itself. The amount of EMG activity recorded in the anal and urethral sphincters at rest was somewhat decreased; high pressures and distinct reflex activity were recorded in both sphincters showing that they escape spinal shock characterized primarily by areflexia. After defining spinal shock a rational explanation based upon neuroanatomical and neurophysiological findings is offered as to why somatic activity of the sacral segments escapes it as evidenced by clincial, urodynamic, and electromyographic recordings.     

Mucoepidermoid odontogenic cyst

This unusual cystic lesion was previously described as a lesion that has features of both botryoid odontogenic cyst and mucoepidermoid tumor and later was named as glandular odontogenic cyst. An additional case is reported and its clinicopathologic features described. The name "mucoepidermoid odontogenic cyst" is proposed.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Growing traumatic leptomeningeal cyst of the roof of the orbit presenting with unilateral exophthalmos

BACKGROUND: Growing skull fractures rarely develop in the skull base region. To the best of our knowledge, only two similar cases have been reported in the English literature. This rare complication, which can occur even after a mild head injury, can produce exophthalmos and threaten the vision. METHODS: The clinical and radiological findings of expanding leptomeningeal cysts extending into the orbit in nine patients referred to the department of Neurosurgery are presented. After appropriate investigations confirming the presence of the expansile retroglobal lesion, surgical exploration was performed via fronto-lateral or the preferred fronto-basal approach. The variable findings are denoted and the relevant literature is also reviewed. RESULTS: Frontobasal head injuries play an important role in pathogenesis of these traumatic expansile leptomeningeal cysts. In this series of nine young girls, 6.65% (six out of nine) injuries happened in the first decade of life with an interval of 2 to 12 months (mean = 6.7, SD = 9.7). High-resolution coronal view computed tomography (CT) scanning with bone density window images, and high intensity cystic lesions visible on T2-weighted coronal MR images were diagnostic clues. CONCLUSIONS: Growing fractures of the anterior skull base may complicate the natural course of healing of any minor frontobasal head injury, especially during childhood. Good quality imaging is mandatory in cases of progressive unilateral exophthalmos. Proper surgical intervention will lead to a good cosmetic result.     

Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis.

PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.     

Pyloric volume: an important factor in the surgeon’s ability to palpate the pyloric “olive” in hypertrophic pyloric stenosis

Objective. The objective of this study was to determine whether the size of the pyloric mass is one of the factors in the surgeon's ability to palpate the pyloric “olive”. Materials and methods. The ultrasonographic images and medical records of 60 infants with surgically confirmed hypertrophic pyloric stenosis (HPS) were reviewed. The pyloric diameter (PD) and pyloric length (PL) were measured and the pyloric volume (PV) was calculated using the equation PV = 1/4π× (PD)²× PL. Based on the pediatric surgeon's physical examination the infants were divided into two groups: those with and those without palpable pyloric masses. Results. Infants with a palpable pyloric mass had an average pyloric volume of 3.33 ± 1.76 mm³, which was statistically larger than those whose hypertrophied pylorus could not be palpated (average volume 2.59 ± 2.07 mm³, P < 0.01). There was no statistically significant age difference between the two groups. Conclusion. Clinical skill of the examiner and other clinical aspects (patient cooperation, etc.) determine palpability of the pylorus in HPS. The size of the hypertrophied pylorus is also an important factor affecting the clinican's ability to palpate the pyloric mass. Received: 29 December 1995 Accepted: 7 June 1996     

Reduction of gait data variability using curve registration

Timing in peak gait values shifts slightly between gait trials. When averaged, the standard deviation (S.D.) in gait data may increase due to this inter-trial variability unless normalization is carried out beforehand. The objective of this study was to determine how curve registration, an alignment technique, can reduce inter-subject variability in gait data without perturbing the curve characteristics. Twenty young, healthy men participated in this study each providing a single gait trial. Gait was assessed by means of a four-camera high-speed video system synchronized to a force plate. A rigid body three-segment model was used in an inverse dynamic approach to calculate three-dimensional muscle powers at the hip, knee and ankle. Curve registration was applied to each of the 20 gait trials to align the peak powers. The mean registered peak powers increased by an average of 0.10±0.13 W/kg with the highest increases in the sagittal plane at push-off. After performing curve registration, the RMS values decreased by 13.6% and the greatest reduction occurred at the hip and knee, both in the sagittal plane. No important discontinuities were reported in the first and second derivatives of the unregistered and registered curves. Curve registration did not have much effect on the harmonic content. This would be an appropriate technique for application prior to any statistical analysis using able-bodied gait patterns.