Experimental purpura and related hematological studies in the hamster.

Thesis (Ph. D.)--Boston UniversityHemorrhagic disorders designated by the term "purpura" are usually associated with the appearance of petechiae, ecchymoses, and lowered platelet counts. However, the mechanism of bleeding and the etiology remain unsolved. The cheek pouch of the hamster was used in an attempt to determine the cause of the bleeding under two conditions: first, in experimental purpura produced by antiplatelet serum prepared by repeated injections of hamster platelets into rabbits, and second, following infusion with dextran. Peripheral blood counts, bone marrow examinations, coagulation tests, and special tests for vascular fragility and hemostatic function (negative pressure, snake venom, and microelectrode) have been applied to normal hamsters as a basis for interpretation in hemorrhagic diathesis. Microscopic observations were made in vivo and recorded on Kodachrome motion picture film by means of cinephotomicrographic equipment. The results of previous blood counts and bone marrow examinations have been confirmed and analyzed more critically. Detailed observations have been made on the morphology of the blood cells in the stained smear and reticulocyte counts have been reported for the first time in the hamster. The red cell count in the hamster (6.8 ± 1.2 million per cu. mm.) is slightly higher than that in man, and the reticulocyte value is also higher (2.5 ± 1.2 per cent). The polymorphonuclear and lymphocytic values were reversed in the hamster (polymorphs 30 ± 6 per cent, lymphocytes 61 ± 7.5 per cent). The peripheral blood smear showed moderate polychromatophilia and occasional target cells. The bone marrow of the hamster was more cellular than that of man, with a ratio of white cells to red cells of 8:1. The coagulation tests were within limits comparable with those for man. Three in vivo tests for vascular fragility and hemostatic function in the hamster cheek pouch were utilized: namely, the moccasin venom test (Fulton, Lutz, Shulman, and Arendt, in press); the negative pressure test (Shulman, Mode, Kagan, and Fulton, Anat. Rec. 118:408, 1954); and the microelectrode test (Fulton, Akers, and Lutz. Blood 8:140, 1953). The snake venom test applied to the cheek pouch of the normal hamster produced 71 ± 6 petechiae at one hour intervals and 138 ± 20 at the end of two hours. The negative pressure test produced from 0 to 4 petechiae at one minute Nith a negative pressure of 20 mm of mercury. The microelectrode test was used to evaluate the fragility of blood vessels by stimulation of the wall with single faradic shocks. Vasoconstriction occurred at low voltages (threshold, 4 to 10 volt single shock) in muscular arterioles and venules. The sphincters were more sensitive than other portions of the vascular network. White cell sticking and platelet thrombosis occurred at higher voltages (10 to 3O volts). The vessel wall of normal hamsters was resistant even to very high voltages (150 volts). If normal vessels were ruptured, the broken ends were sealed immediately, probably by "electrocoagulation". The results of the microelectrode test were compared in young and "old age" hamsters. No significant differences were obtained except for an increase in white cell adhesiveness in the "old age" group. Hamsters of either sex and 75 to 100 grams in weight were splenectomized. The platelet counts increased daily for 4 to 6 days after splenectomy and gradually returned to normal on the 14th to 18th day. The smear of peripheral blood exhibited increased polychromatophilia, target cells, and clumps of platelets, particularly on the 4th to 8th day. Howell-Jolly bodies were absent. Changes in the bone marrow were not remarkable. The microelectrode test for thrombus susceptibility revealed a marked tendency for thrombosis, while the fragility threshold did not differ from that in normal hamsters. Experimental thrombocytopenic purpura in hamsters, caused by injection of antiplatelet serum, produced spontaneous purpura, ecchymoses and bleeding manifestations in the cheek pouch and in almost all organs of the body. The platelet counts were decreased and the bone marrow showed immature-like amorphic megakaryocytes. Bleeding times and clot retraction determinations were abnormal. Values for the bleeding time in excess of 240 seconds v-rere not uncommon (normal bleading time, 109 ± 19). The snake venom test produced profuse numbers of petechiae within one half hour. Stimulation of the blood vessel wall with low voltage produced platelet thrombi in normal hamsters. In thrombocytopenic hamsters, thrombus formation and leukocytic sticking did not occur even with high voltages. However, the vessel walls were fragile and rupture occurred at electric thresholds lower than 150 volts (60 to 140). These changes were more marked at 24 hours after treatment with antiplatelet serum than at two hours. Small repeated injections of antiplatelet serum produced similar results. In control experiments, hamsters were injected with serum obtained from normal rabbits and with saline solution. The test procedures showed no appreciable deviations from normal values. The fragility thresholds were normal. The splenectomized hamsters with elevated platelet counts were given antipletelet serum. The fragility threshold to electrical stimulation of the vessel wall was lowered and hemorrhage occurred at low voltages. Consequently, splenectomy and the concomitant increase in numbers of circulating platelets shed no protective effect in experimental purpura. Recently, detrimental reactions to plasma substitutes have been critically evaluated and the dextrans have been reported to cause a hemostatic defect in human beings. Dextran increased the bleeding time in normal volunteers as well as in patients with shock. The exact nature of the bleeding phenomenon has not been determined. The precise techniques available for the study of hemorrhage in the hamster cheek pouch have been used to evaluate the hemostatic defect caused by dextran and to observe in vivo the changes occurring in the formed elements of the blood end in the characteristics of the vessel wall. Hematological changes in the hamster after infusion with dextran were insignificant except for the effects of hemodilution and the clumping of platelets. The results of the various coagulation tests (clotting time, prothrombin time, clot retraction, and fibrinolysis test) were within normallimits. The bleeding time was prolonged significantly as shown by values of more than 240 seconds as compared with values of 109 ± 19 seconds in normal hamsters. All dextrans used in this study (Lares, Cutter) produced an increased bleeding time except Expandex. The Lares dextran seemed to be more detrimental than other types. After injection of Lares, increased numbers of leukocytes were adherent to the endothelium at 24 hours and during a period of 3 to 4 weeks. The thrombosis threshold was increased. The formation, canalization, and embolization of thrombi were recorded on Kodachrome motion picture film. The frag ility threshold, as tested with microelectrode and also snake venom, was lowered. The vascular defect was greater with Lares than with other dextrans. In conclusion, experimental purpura was produced in hamsters by antiplatelet serwn for the first time. The resultant bleeding phenomenon and hemostatic defect was related to lowered platelet counts and decreased frag ility of the vessel wall. Splenectomy accompanied by increased platelet counts was not remedial. The effects of dextran infusions in hamsters have been critically evaluated by routine hematological tests and by special tests for vascular fragility and hemostatic function. A defect in the vessel wall was shown by the lowered fragility to faradic stimulation. This finding provided the basis for a new explanation for the hemostatic defect, namely, damage to the vessel wall. This is in addition to the previously known factors of prolonged bleeding time and unexplained clumping of the platelets

Measuring Presence in a Police Use of Force Simulation

We have designed a simulation that can be used to train police officers. Digital simulations are more cost-effective than a human role play. Use of force decisions are complex and made quickly, so there is a need for better training and innovative methods. Using this simulation, we are measuring the degree of presence that a human experience in a virtual environment. More presence implies better training. Participants are divided into two groups in which one group performs the experiment using a screen, keyboard, and mouse, and another uses virtual reality controls. In this experiment, we use subjective measurements and physiological measurements. We offer a questionnaire to participants before and after play. We also record the participants change in heart rate, skin conductivity and skin temperature using Empatica device. By comparing the data collected from both groups, we prove that people experience more presence in the virtual environment

Measuring Presence in a Police Use of Force Simulation

We have designed a simulation that can be used to train police officers. Digital simulations are more cost-effective than a human role play. Use of force decisions are complex and made quickly, so there is a need for better training and innovative methods. Using this simulation, we are measuring the degree of presence that a human experience in a virtual environment. More presence implies better training. Participants are divided into two groups in which one group performs the experiment using a screen, keyboard, and mouse, and another uses virtual reality controls. In this experiment, we use subjective measurements and physiological measurements. We offer a questionnaire to participants before and after play. We also record the participants change in heart rate, skin conductivity and skin temperature using Empatica device. By comparing the data collected from both groups, we prove that people experience more presence in the virtual environment

High-risk sexual behaviour among HIV–negative MSM in England: behavioural data to inform HIV prevention

This thesis would not have been possible without Fiona Burns and Anthony Nardone, my two main supervisors. They have been there every step of the way, always patient and always ready to read another draft of the thesis chapters. I have learnt so much from them. They have contributed hours of reading and somehow managed to always come back with constructive and supportive feedback. I also cannot thank them enough for their moral support. They have understood the challenges associated with meeting the demands of the PhD and raising a young family and have helped me get through those moments where it all felt too challenging. I would also like to thank Graham Hart and Noel Gill, my other supervisors. They have both been there to ask the right questions including the “so what?” question, to challenge me and ensure the PhD was on the right track. Their combined guidance and oversight has been invaluable to this thesis. It has been a pleasure to work with them. I would like to thank all of my collaborators and colleagues for their insights and contributions over the years. It has been my privilege to work with all these individuals and teams both within UCL and Public Health England but also those beyond. The HIV team have been patient with my part-time working arrangements while the GUMCAD team have had to endure endless questions about the surveillance system. I also want to thank those who participated in the behavioural study. It was not an easy endeavour but thank you for being enthusiastic and persevering. Special thanks go to Menelaos Pavlou for his support and patience with all my questions about risk predictions models. Thanks also go to Carina and Maryam for the joint efforts in the SANTE project and to Maryam for sharing her knowledge of the viva. It has also been a pleasure to share the PhD journey with Sarah, Ellie, Ibi, Jess, Vicky, Meaghan, Sara, Adamma and David. Your inputs and support have enriched my PhD experience! Thank you. I would like to thank my family and friends who have been brilliant with their encouragements, and sometimes much required pep talks. I especially want to thank my family for being there and ungrudgingly providing child care when the PhD took over my life. And finally, to Anil: you have been unwavering, patient and supportive beyond what words can describe. Thank you for taking charge at bath- and bedtimes and keeping me supplied with food and drink. I am grateful (and probably quite a lucky girl!) that you have been by my side through this journey

Factors influencing preparation needed of future industrial technology department leaders in higher education

The object of this study was to help future industrial technology department leaders in higher education develop effective planning strategies and prioritize their preparation before they sought leadership positions in industrial technology. Two hundred fifty-four industrial technology department leaders in higher education from all over the United States were asked to respond to a questionnaire. A five point Likert-type scale was used to rate the importance of 58 statements identified from Marshall\u27s (1984) study. One hundred sixty (62.99%) usable responses formed the basis of this study. Mean values and standard deviations were determined for all the statements. The grand mean was used to identify important statements. The two-tailed t test for independent means was used to determine significant differences identified in the research questions. Thirty-one of the 58 activity statements had a mean value greater than the grand mean of 3.893. Funding had six important activity statements, followed by personnel, curriculum, and administration with five each, technology/change with four, external relations and recruitment with three each, and department designation without any important activity statement. It was concluded that there was a significant difference in the perceptions of newer department leaders and more experienced department leaders regarding important activities. Also, use of computers was more important to department leaders with only undergraduate programs, whereas research was more important to department leaders who also had graduate programs. Department leaders in large departments wanted a partnership with industry for curriculum input, whereas department leaders in small departments were more concerned in ensuring that an appropriate range of programs and offerings were available. Identification of external sources of funding was more important to department leaders in public institutions. Providing leadership in establishing and maintaining program accreditation was important to leaders in predominantly ($\u3e$50%) minority institutions

Puffy Foot Syndrome: An Important Often Overlooked Clinical Entity

The puffy foot syndrome, a novel clinical entity, describes the complication of secondary lymphedema with chronic progression in the feet, a finding that has often been overlooked in the non-tropical setting. While previously well described in the upper extremities, this complication has not been fully explored in the lower extremities. However, given increasing rates of diabetes mellitus, obesity, and a myriad of other possible etiologies in the United States, it is important to understand this entity and its non-viral, non-parasitic causes in non-tropical regions. This review delineates common illustrative properties of this syndrome observed in clinical practice as well as long-term complications, including Ruocco’s immunocompromised cutaneous district, that are often overlooked. Furthermore, a novel method of staging is suggested for this condition, reflective of increasing risk of complication, infection, and malignancy. We also highlight the increased need for improved detection and recognition of this condition to avoid possibly deleterious outcomes

Puffy Foot Syndrome: An Important Often Overlooked Clinical Entity

The puffy foot syndrome, a novel clinical entity, describes the complication of secondary lymphedema with chronic progression in the feet, a finding that has often been overlooked in the non-tropical setting. While previously well described in the upper extremities, this complication has not been fully explored in the lower extremities. However, given increasing rates of diabetes mellitus, obesity, and a myriad of other possible etiologies in the United States, it is important to understand this entity and its non-viral, non-parasitic causes in non-tropical regions. This review delineates common illustrative properties of this syndrome observed in clinical practice as well as long-term complications, including Ruocco’s immunocompromised cutaneous district, that are often overlooked. Furthermore, a novel method of staging is suggested for this condition, reflective of increasing risk of complication, infection, and malignancy. We also highlight the increased need for improved detection and recognition of this condition to avoid possibly deleterious outcomes

A Comparative Evaluation of Salivary Changes and Oral Indices in Pediatric Patients Having Chronic Kidney Disease and Juvenile Diabetes with Healthy Controls

Background and Aim: Chronic Kidney disease is a common condition seen in Juvenile diabetes with 90% of renal impairment patients displaying a wide spectrum of oral manifestations in the hard and soft tissues including changes of the salivary composition and flow rate. There is an increase in the serum cystatin-C, urea and creatinine levels in these patients, which is reflected in the saliva. This study was conducted to assess the changes in salivary levels of cystatin-C, urea, and creatinine as well as oral – Decayed, Missing and Filled Teeth Index (DMFT) and gingival indices in pediatric patients suffering from chronic renal disease and juvenile diabetes and compare them with healthy individuals.Methods: Fifteen patients with juvenile diabetes suffering from chronic renal disease and 15 healthy controls aged 2-18 years were included in the study. Their saliva was analyzed for creatinine, cystatin-C and urea levels using an auto-analyzer and correlated with their existing serum levels. DMFT, gingival index, gingival bleeding and gingival enlargement indices were also assessed. Results: Increased levels of salivary cystatin C, urea (p value <0.001) and creatinine (p value =0.001) were seen in the cases. The deft value was significantly lower (p value <0.001) while the gingival index, gingival bleeding index, and gingival enlargement index were significantly higher in the subjects with renal impairment.  Conclusion: Chronic Kidney disease results in many metabolic changes in the body, necessitating frequent biochemical blood analysis. Saliva, being a non-invasive, simple and rapid adjunctive tool, can be used for diagnosing and staging the disease and to check the progression of the condition.Keywords: Chronic Kidney Disease; Renal Dysfunction; Saliva; Cystatin-C; Diagnosis

Stochastic Optimization to Reduce Aircraft Taxi-in Time at IGIA, New Delhi

Since there is an uncertainty in the arrival times of flights, pre-scheduled allocation of runways and stands and the subsequent first-come-first-served treatment results in a sub-optimal allocation of runways and stands, this is the prime reason for the unusual delays in taxi-in times at IGIA, New Delhi. We simulated the arrival pattern of aircraft and utilized stochastic optimization to arrive at the best runway-stands allocation for a day. Optimization is done using a GRG Non-Linear algorithm in the Frontline Systems Analytic Solver platform. We applied this model to eight representative scenarios of two different days. Our results show that without altering any physical infrastructure and using this stochastic simulation model, there is a potential 38.97% improvement in the average taxiing time of the arriving aircraft, assuming a constraint of simultaneous arrivals of two aircraft within a minute. A simulated run optimization technique, if applied at the IGIA, would produce huge savings in passengers’ time, additional fuel costs, and, after all, environmental degradation

A case of inferior lumbar hernia

In this article we report a case of inferior lumbar hernia. The patient underwent preperitoneal meshplasty. The patient is well on follow up with no recurrence. The relevant literature has been reviewed and management discussed in brief