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Purpose The aim of this article is to examine the association between industry payments to ophthalmologists and scholarly impact. Design Retrospective cross-sectional study. Methods All ophthalmology faculty at United States accredited ophthalmology residency programs were included in this study. The main exposure was industry payments to ophthalmologists in 2016, as reported in the Centers for Medicare and Medicaid Services Open Payments Database. The primary outcome was Hirsch index (H-index), a measure of scholarly impact. Results Among 1,653 academic ophthalmologists in our study, 1,225 (74%) received industry payments in 2016. We did not observe a difference between the mean H-index of ophthalmologists receiving any industry payments versus those not receiving any payments (p = 0.68). In analysis including only ophthalmologists who received industry payments, H-index differed significantly by payment amount: 12.6 for ophthalmologists receiving less than $100, 12.2 for those receiving $100 to 1,000, 18.8 for those receiving $1,000 to 10,000, 21.3 for those receiving $10,000 to 100,000, and 29.4 for those receiving greater than $100,000 (p Conclusions Although our analysis cannot prove causality, we observed a significant association between industry payments and scholarly impact among academic ophthalmologists, even after adjusting for gender, academic rank, and subspecialty. Prospective studies should further evaluate this relationship.

Purpose The current demographics of the ophthalmology workforce do not reflect the diverse United States population, which has implications for addressing health disparities. The demographics of ophthalmology department faculty may influence the recruitment of underrepresented students into the field. This study sought to determine how the racial and ethnic demographics of ophthalmology department faculty compare with those of other clinical departments at United States medical schools. Design Secondary data analysis of medical school faculty demographic data from the 2019 American Association of Medical Colleges (AAMC) Faculty Roster. Participants Clinical faculty and department chairs at United States medical schools. Methods We analyzed the racial and ethnic demographics of clinical department faculty and department chairpersons using data from the 2019 AAMC Faculty Roster. We calculated the proportion of underrepresented minority (URM) faculty in ophthalmology and in 17 other clinical departments. We analyzed these data for statistically significant differences between ophthalmology and other clinical departments. In addition, we compared the percentage of URM ophthalmology faculty with the proportion of URM persons among graduating United States medical students and in the United States population using data from the Medical School Graduation Questionnaire and the United States census, respectively. Main Outcome Measures The proportion of URM persons, defined as Black, Hispanic or Latino, Native American, or Native Hawaiian or Pacific Islander among clinical faculty and department chairs. Results Ophthalmology faculty are less racially and ethnically diverse than graduating medical students and the general United States population. When compared with 17 other clinical departments, ophthalmology has the third-lowest proportion of URM faculty, with only radiology and orthopedic surgery having a smaller proportion of URM faculty. These differences were statistically significant in most departments (12 of 18). No statistically significant difference was found in the proportion of URM department chairs in ophthalmology compared with most other clinical departments, although the absolute number of URM chairs in ophthalmology is low at only 8 chairpersons. Conclusions More work must be done to increase the recruitment of URM physicians into ophthalmology faculty positions to obtain parity with other clinical departments and with the diverse patient populations that physicians serve.

Medical students must gain proficiency with the complex skill of case presentations, yet current approaches to instruction are fragmented and often informal, resulting in suboptimal transfer of this skill into clinical practice. Whole task approaches to learning have been proposed to teach complex skill development. The authors describe a longitudinal case presentation curriculum developed using a whole task approach known as four-component instructional design (4-C/ID). 4‑C/ID is based on cognitive psychology theory, and carefully attends to titrating a learner’s cognitive load, aiming to always keep students in their zone of proximal development. A multi-institutional group of medical educators convened to develop expert consensus regarding case presentation instruction using the 4‑C/ID model. A curriculum consisting of 1) learning tasks, 2) supportive information, 3) just-in-time information, and 4) part-task practice was developed. Domains were identified that make the task of delivering a case presentation complex. A simplifying conditions approach was applied to each domain to develop sequential task class descriptions. Examples of the four components are given to facilitate understanding of the 4‑C/ID model, making it more accessible to medical educators. Applying 4‑C/ID to curriculum development for the complex skill of case presentation delivery may optimize instruction. The provision of the complete curricular outline may facilitate transfer and implementation of this case presentation curriculum, as well as foster the application of 4‑C/ID to other complex skill development in medical education. Electronic supplementary material The online version of this article (10.1007/s40037-018-0443-8) contains supplementary material, which is available to authorized users.

Partial discharge measurements have been used for studying shrinkage voids in the insulation of mass-impregnated high voltage DC subsea power cables. Three 4.5-m long cable samples were subjected to ac partial discharge measurements at different ambient temperatures, both under isothermal conditions and after load current turnoffs. Two distinctly different phase resolved partial discharge patterns were observed, suggesting that two different "types" of cavities were created. The type causing by far the most powerful discharges appeared a few hours into the cooling period after load turn-off, which coincides in time with when load cycling breakdowns during type testing usually occur. Current loading has a significant effect on the cavities, as it leaves them – at least temporary – with a different dielectric strength afterwards. The mechanisms behind this change are not identified, but the associated time constants are of the order of days and weeks. Consequently, accurately determining the limitations of such cables with regard to their ability to withstand polarity reversals and rapid load changes may be more complicated than previously assumed. Cavities in Mass-Impregnated HVDC Subsea Cables Studied by AC Partial Discharge Measurements

Problem Health disparities among racial and ethnic groups exist in the United States despite improvements in health status and access to care. These inequalities may be reduced by increasing minority physician recruitment; however, how best to recruit these physicians remains unclear. Approach Near-peer teachers are not professionally trained, but have recently learned material that they themselves teach. Near-peer teaching in minority student outreach programs may be effective in increasing minority physician recruitment. The authors used a near-peer teaching model to promote interest in medicine, specifically ophthalmology, as a potential career path for both volunteer near-peer teachers and minority high school students participating in an educational outreach program. Twenty-one college and graduate-school near-peer teachers of various racial and ethnic backgrounds participated to teach 31 inner-city high school students. The program was evaluated using pre- and posttest surveys assessing students' knowledge about and interest in science, medicine, and ophthalmology; analysis used pairwise t-test comparisons. Qualitative responses and an end-of-training survey also assessed students' and near-peer teachers' satisfaction with the program and perceptions about medicine as a career. Outcomes Students' knowledge about and interest in medicine and ophthalmology increased significantly after participation. Near-peer teachers agreed that teaching in the program was beneficial to their careers and made it more likely that they would enter medicine and ophthalmology. Next Steps The authors will track the near-peer teachers' career paths and, in the next iteration, will increase the number of program days. This intervention may serve as a model for outreach for other specialties beyond ophthalmology.

To determine if receiving a prescheduled appointment is associated with an increased likelihood of complying with follow-up eye care among individuals identified as at risk for glaucoma during community-based glaucoma screening in an urban underserved population. This study sampled 362 individuals aged ≥30 years without known glaucoma from low-income, predominantly black/Hispanic neighborhoods in New Haven, Connecticut presenting to one of twelve community-based glaucoma screening events from May 2010 to October 2012. A quasi-experimental design systematically assigned 63 individuals identified as at risk for glaucoma into either intervention or control group with a 1:2 ratio. Individuals in the control group (n = 41) received counseling on glaucoma and a recommendation for obtaining a follow-up appointment at the eye department of a local community health center, which offers affordable health services with income-adjusted fee discounts to uninsured, low-income patients. Those in the intervention group (n = 22) received the same counseling and a prescheduled appointment at the community health center. The overall rate of follow-up compliance within 3 months of screening was 30 % (41 % in the intervention group; 24 % in the control group). Multivariate logistic regression analysis adjusting for sex, age, ethnicity, health insurance status, car access, living situation, and smoking status found that follow-up compliance was significantly associated with intervention (adjusted odds ratio 4.8; 95 % confidence interval 1.1-20.9). Providing prescheduled appointments can improve follow-up compliance after community-based glaucoma screening. This finding may be potentially applicable to community-based health screening for other preventable diseases.

To identify barriers to follow-up eye care in children who failed a visual acuity screening conducted by their primary care provider.Children aged 3-14 years who failed a visual acuity screening were identified. A phone survey with the parent of every child was conducted 4 months after the screening. Family demographics, parental awareness of childhood eye diseases and eye care for children, and barriers to follow-up eye care were assessed.Of 971 children sampled, 199 (20.5%) failed a visual acuity screening. The survey was completed by the parents of 58 children (29.1%), of whom 27 (46.6%) presented for follow-up examination. The most common reason for failure to follow-up was parental unawareness of screening results (29.3%). Follow-up rates were higher in children with previous eye examinations than in those without (81% versus 17%; P = 0.005) and in children who waited2 months for a follow-up appointment than in those who had to wait longer (100% versus 63%; P = 0.024). Child's sex, ethnicity, and health insurance status, parent's marital, education and employment status, household income, and transportation access were not associated with statistically significant different follow-up rates.Parental unawareness of a failed visual acuity screening is an important barrier to obtaining follow-up. Strategies to improve follow-up rates after a failed visual acuity screening may include communicating the results clearly and consistently, providing education about the importance of timely follow-up, and offering logistic support for accessing eye appointments to families.

Short spall propagation times of failing main shaft ball bearings of aircraft engines are a serious safety concern for single engine aircraft. Bearing designers would like to understand the impact of four variables namely (i) ball material density, (ii) subsurface residual stress, (iii) gradient in yield strength with depth (case hardening), and (iv) raceway surface hardness/yield strength that are thought to affect spall propagation. Extensive spall propagation experiments have been conducted at AFRL, Ohio in the past few years to address this issue. However, a detailed mechanistic analysis of these experiments has not been performed. This work presents an elastic–plastic finite element (FE) model that simulates a ball impacting a spall edge to determine the relative contributions of the four material variables on spall propagation. The magnitude and extent of damage of the spall edge material is determined based on critical stresses and plastic strains induced by the ball impact. The results indicate that the influence of ball density is greatest on inducing damage at the impacted spall edge when compared to the other three properties, which also agrees with the hybrid bearing spall propagation tests conducted at AFRL.

The recent results of Protocol T have illustrated the efficacy of aflibercept in the treatment of diabetic macular edema. It also demonstrated that in patients with poor vision (

Objective:To evaluate the effect of education sessions on Indian schoolteacher awareness of childhood eye health issues, responsibility for children’s eye health, and successful participation in a teacher-led eye screening health intervention programme in primary schools aimed at addressing avoidable childhood blindness in India.Design:Quantitative study, pre-intervention and post-intervention surveys and questionnaires.Setting:One hundred and four government-employed schoolteachers in primary schools of Hyderabad, India.Method:Prior to the screening intervention programme, questionnaires were administered to evaluate baseline teacher knowledge and observed responsibility for management of children’s eye health. The intervention consisted of three one-hour educational training sessions at central community locations about children’s eye health and proper screening practices, followed by on-site monitoring of teacher screenings after a period of 10 school days. Post-programme questionnaires and surveys were administered to evaluate changes in knowledge and attitudes.Results:Despite low levels of pre-programme knowledge and felt responsibility, teachers demonstrated significant improvements in overall knowledge of eye parts and functions, common childhood diseases, and local myths (39.3% to 63.7%, p < 0.01) and significant increases in felt responsibility for children’s eye health (45.5% to 77.8%, p < 0.01) through the course of the programme.Conclusion:Apart from technical training, educational sessions may play an important role in promoting sustained teacher interest in school-based health intervention programmes and overall impact on community health. Urban schoolteachers have therefore been identified as promising candidates in the continued effort to eliminate avoidable childhood blindness in India and other parts of the developing world.

The ESA (European Space Agency) Sentinel-5 Precursor (S-5 P) is a low Earth orbit polar satellite to provide information and services on air quality, climate and the ozone layer in the timeframe 2015-2022. The S-5 P mission is part of the Global Monitoring of the Environment and Security (GMES) Space Component Programme. The payload of the mission is the TROPOspheric Monitoring Instrument (TROPOMI) that will measure key atmospheric constituents including ozone, NO2, SO2, CO, CH4, CH2O and aerosol properties. TROPOMI has heritage to both the Ozone Monitoring Instrument (OMI) as well as to the SCanning Imaging Absorption spectroMeter for Atmospheric CartograpHY (SCIAMACHY). The S-5 P will extend the data records of these missions as well as be a preparatory mission for the Sentinel-5 mission planned for 2020 onward. The mission is pre-operational and is the link between the current scientific and the operational Sentinel-4/-5 missions. This contribution describes the science and mission objectives, the mission and the instrument, and the data products. While building on a solid foundation of the heritage instruments, the S-5P/TROPOMI mission is an exciting step forward with a strong focus on the troposphere. This is achieved by a combination of a high spatial resolution and improved signal-to-noise, as well as dedicated data product development. It is anticipated that the S-5 P mission will make a large contribution to the monitoring of the global atmospheric composition, as well as to the scientific knowledge of relevant atmospheric processes. © 2012 Elsevier Inc.

The need for higher performance in jet turbine engines has led to the development of alloys with greater hardness for use in bearings. The increased hardness is a result of carburizing of the surface which leads to a change in the surface chemistry through the formation of metal carbides. The authors have found that metal carbides react differently with the lubricants and additives than the oxides found on the surface of currently used alloys. Of particular concern is the observed reaction of the ester basestock with metal carbides in the presence of phosphate esters. The authors have found that metal carbides can catalyze the decomposition of hindered esters in the presence of aryl phosphates to give the component acids. Products of the reaction include free acids, phenyl esters, and dehydrogenated esters. This reaction is expected to rapidly degrade the performance of the oil due to both acid formation and viscosity breakdown. Examination of the remaining solid material indicates that phosphorus has been incorporated into the structure, presumable as phosphate.

133 mm bore ball bearings with silicon nitride rolling elements were tested at the following conditions: speeds from 1.5 to 2.6 × 106 DN; thrust loads from 13,350 to 53,400 N; oil delivery temperatures from 66 to 121°C; and oil flow rates from 7.3 to 11.4 L/min. The resulting bearing outer race temperature, oil exit temperature, power loss determined from shaft torque, and power loss determined from oil temperature rise are reported. The experimental data are fitted to an empirical equation to predict power loss. The results are compared to the same bearings fitted with metal rolling elements discussed in Part I.

The effect of the oil anti-wear additive tricresyl phosphate (TCP) on rolling contact fatigue (RCF) life of advanced bearing steels—AISI VIMVAR M50, CSS 42L, Pyrowear 675, and Cronidur 30 was investigated with silicon nitride balls at 177 °C and at a maximum Hertzian stress of 5.5 GPa. TCP at 1% additive concentration was blended into a synthetic polyol ester turbine engine lubricant basestock having a nominal viscosity of 3 cSt at 100 °C. Additionally, the basestock was fortified with the anti-oxidants dioctyl-diphenyl amine (DODPA) and phenyl-α-napthyl amine (PANA) at 1% concentration each. The presence of TCP has a measurable positive effect on RCF life and wear. Also, all the advanced bearing materials exhibited superior fatigue life compared to conventional bearing steel M50, both with and without TCP. The study indicates that current gas turbine lubricant formulations with TCP have positive effects on fatigue life and wear performance of M50, Pyrowear 675, CSS 42L, and Cronidur 30.

State-of-the-art bearing materials, such as Pyrowear 675(P675) have been developed to meet the requirements of the next generation of gas turbine engines. P675 bearings have exhibited higher land wear compared to conventional M50 bearings under contaminated test conditions. Surface modification techniques can be applied to enhance the wear resistance of bearing land surfaces. A coating has been developed to minimize abrasive wear of land surfaces. A new procedure using a 40 mm bearing test rig has been developed to effectively evaluate land wear under simulated contaminated condition. Test conditions including contamination concentration, test duration, test temperature and lubricant flow rate were optimized to obtain measureable wear on the land surfaces in a reasonable test time. Results obtained using M50 Nil, P675 and M50 bearings are presented to illustrate the viability of the test procedure.

ObjectivesAccording to an estimated mesh shrinkage following hernia repair of up to 40% a current dogma in hernia surgery requires a mesh overlap of 5 cm around the hernia. However, no valid data addressing this problem of mesh shrinkage are available at present.Patients and methodsWithin the framework of a prospective randomized double-blinded clinical trial, 50 patients were operated on for a ventral abdominal hernia with the open sublay technique using specially prepared radio-opaque polypropylene (PP) meshes. Of the patients 27 received a conventional heavyweight mesh (P group) and 23 a new lightweight mesh construction (NK group). Follow-up for at least 2 years after mesh repair included conventional abdominal x-rays after 7 days, 3 weeks and 4, 12 and 24 months, as well as computed tomography after 7 days and 4 and 12 months. Main criteria were mesh shrinkage, recurrence and complication rates and quality of life comparing groups P and NK.ResultsIn 46 cases (92%) no mesh shrinkage could be detected and only 4 meshes (8%) showed a moderate shrinkage (1 of 22.2%, 2 of 8% and 1 of 3%) all from the P group. While no hernia recurrences were found, 2 surgical complications occurred with 1 seroma in the P group and 1 hematoma in the NK group. Quality of life showed a linear improvement over time up to the 2 year time point following mesh repair with advantages for the NK group. Pain and mobility scores reached standard values 12 months postoperatively without significant differences between the two groups.ConclusionsIn principle PP meshes following an uncomplicated ventral hernia repair do not shrink at all. A moderate shrinkage in isolated cases might occur following heavyweight mesh implantation. Under controlled conditions recurrence as well as complication rates are equal for heavyweight and lightweight PP meshes. Quality of life improves up to 2 years following mesh repair with a trend to a better outcome for lightweight meshes. Pain and mobility scores reached standard values 12 months postoperatively without significant differences between the lightweight and heavyweight meshes.

This article is the first part of a three-part series that investigates the rolling contact fatigue (RCF) initiation and spall propagation characteristics of three bearing materials, namely, AISI 52100, VIM-VAR AISI M50, and VIM-VAR M50NiL steels. Although there is substantial prior work published on the rolling contact fatigue initiation of these materials, little has been published on their spall propagation characteristics after spall initiation. It is recognized that rapid spall growth can lead to catastrophic bearing failure. Hence, understanding the spall growth phase and factors that may cause accelerated growth rates is key to achieving a reliable and robust bearing design. The end goal is to identify control parameters for optimizing bearing materials for improved spall growth resistance. This first part study features the experimental results from 208-size (40 mm bore) angular-contact ball bearings endurance life tested at maximum Hertzian contact stress levels of 3.10 GPa and bearing outer race...

This is the third part of a three-part series that investigates the rolling contact fatigue initiation and spall propagation characteristics of three bearing materials, namely, AISI 52100, VIM-VAR M50, and VIM-VAR M50 NiL steels. Though there is substantial prior work published on the rolling contact fatigue initiation of these materials, little is known about their spall propagation characteristics after spall initiation. In Part III, 208-size, 40-mm-bore bearings are examined for changes in appearance of the microstructure as well as residual stress as a function of depth in the circumferential direction. The correlations between the experimental results from Part I and computer modeling in Part II are made.

This is the second part of a three-part series that investigates the rolling contact fatigue initiation and spall propagation characteristics of three bearing materials, namely, AISI 52100, VIM-VAR M50, and VIM-VAR M50NiL steels. A systematic investigation of the effects of rolling contact fatigue (RCF) on the evolution of material properties and microstructural changes resulting in spall propagation rate has not been conducted. As a first step toward understanding spall propagation, we present stress distribution in the neighborhood of a spall initiated by RCF by an indent on a hybrid 40-mm ball bearing. Elastic and elastic-plastic subsurface stress fields are computed using finite element models that incorporate the full three-dimensional (3D) ball-raceway geometry. The stress fields predicted indicate extensive yielding around the spall edges. The spall is shown to widen first axially across the width of the raceway, causing the ball to unload as it enters the spall. The effect of the potential impact ...

Carbamazepine and dipyridamole are class II compounds (BCS) whose oral bioavailability is limited by poor solubility. The use of glass solutions to improve the bioavailability of this class of compound has been an area of research for a number of years. The influence of polymer parameters (Tg, hydrophilicity, solubility parameter, and ability to hydrogen bond) on glass solution properties is investigated.Carbamazepine and dipyridamole glass solutions are prepared with PVP/VA 64 and PVP/VA 37 by spray drying and melt extrusion. The products are then characterized by XRPD, thermal, and spectroscopic methods. Yield, physical stability, and dissolution profiles are also assessed.The properties of the polymer greatly influenced the ability to produce glass solutions. With decreases in Tg and hydrophilicity, melt extrusion became the more viable of the two preparative techniques. Although glass solutions were successfully prepared, the greater the difference in component solubility parameter, the less physically stable the formulation.Consideration must be given to the characteristics of the polymer when selecting for glass solution formulation. Although a number of process parameters can be varied for melt extrusion and spray drying, their ability to overcome fundamental differences in the physical parameters discussed is limited.

Objective Resident physicians have reported spending upward of 25% of their time teaching fellow residents and medical students. Until relatively recently, there have not been formal requirements in residency programs to learn teaching skills. The first goal of this study was to develop a novel residents-as-teachers training program to educate Ophthalmology residents on facilitating group learning and emphasizing critical-thinking skills. The second goal was to educate residents on how to teach clinical reasoning skills. Design We designed a longitudinal residents-as-teachers program that consisted of a 2-hour workshop, voluntary observation of their teaching in the small group, and student feedback on their teaching. The focus of the workshop was to educate the residents on how to facilitate critical thinking and clinical reasoning in a small group format. Voluntary video recording of residents’ teaching was offered, and feedback on their teaching was provided. Setting Yale University School of Medicine, Department of Ophthalmology and Visual Science. Participants In total, ten second-year medical student groups consisting of approximately 7 to 11 students in each group were organized in this course and each group had one teacher: 4 senior Ophthalmology residents and 6 community faculty. Results This study found that the resident teachers who completed the residents-as-teachers program were equally as effective as community faculty teachers in building medical students’ comprehension of ophthalmic principles during small group seminars according to the students’ evaluation of teaching performance. We also found that all of the medical students’ responses were overwhelmingly positive toward having residents as teachers. The medical students particularly noted residents’ preparedness and effectiveness in facilitating a discussion during the small group seminars. Conclusions Our novel program was effective at teaching residents how to teach critical-thinking skills and the resident teachers were well received by medical students in the classroom. Given the requirement that residents learn teaching skills during residency and our preliminary success, we plan to continue inviting residents to teach small group seminars in Ophthalmology, and we will continue to provide them with the residents-as-teachers program.

This study invited a cross-sectional sample of 112 homeless/marginally housed adults in New Haven, CT to respond to a structured survey questionnaire. Seventy-six individuals responded. Among them, 39 (51%) had utilized primary care services during the preceding 2 years. Multivariate logistic regression analysis adjusting for age, sex, ethnicity, housing status, health insurance status, and self-reported health status found that having utilized primary care services was significantly associated with having regular contact with a community health nurse. This finding indicates that community health nurses may have a significant influence in increasing primary care service utilization by homeless and marginally housed individuals.

Current treatment options for advanced metastatic melanoma are limited to experimental regimen that provide poor survival outcomes. Immunotherapy is a promising alternative and we recently reported a clinical trial in which 6 out of 19 patients enrolled had objective clinical responses to a fully autologous melanoma/dendritic cell vaccine. The mechanism of the vaccine is not well understood, but we hypothesized that general immunocompetence may be a determinant of clinical response. We therefore examined the immune status of an expanded series of 21 patients who displayed varying clinical responses to the melanoma/dendritic cell vaccine. Immunocompetence was assessed using in vitro assays of lymphocyte function: survival, proliferation and cytokine responses to mitogen stimulation as well as T-cell receptor zeta expression and lymphocyte subset analysis. Although lymphocytes from patients mostly performed comparably to age-matched and sex-matched controls, in some assays we identified significant differences between complete clinical responders and other patients, both before and following vaccination. Surprisingly, before vaccination, only lymphocytes from clinical responder patients showed impaired in vitro survival. Following vaccination, T lymphocyte survival improved and cells recovered their ability to produce the Th1-associated cytokines TNF and IFN-gamma in response to anti-CD3 stimulation in vitro. No increase in Th1 cytokine production was observed in lymphocytes from patients who experienced partial clinical responses or progressive disease. We conclude that, before vaccination, patients who go on to have complete responses have immune characteristics suggestive of high cell turnover and low Th1-associated cytokine production, and that these can be reversed with vaccination. These results have potential implications for future immunotherapeutic strategies.

A number of studies in the literature have reported on the use of different preparative techniques to convert crystalline pharmaceutical compounds into the amorphous form. However, very few direct comparisons of different preparative techniques using the same drugs are available. The purpose of this study was to determine the influence of two techniques: quench cooling and ball milling on four structurally diverse pharmaceutical drugs. Dipyridamole, carbamazepine, glibenclamide, and indomethacin were converted to the amorphous form by (a) quench cooling of the drug melt and (b) ball milling. The chemical purity and physical form of the products was determined using diffractometric, spectroscopic, and thermal analytical techniques. Products were analysed immediately post preparation and after storage under different stability conditions. Quench cooling of the melt resulted in amorphous conversion of all four compounds. However with glibenclamide, quench cooling resulted in unacceptable chemical degradation whereas ball milling of glibenclamide resulted in a change in the keto-enol tautomerism at the aryl amide moiety of this drug. Ball milling resulted in predominantly amorphous products for all compounds except carbamazepine. Ball milling of carbamazepine resulted in a polymorphic transition of the starting material to form III. Physical stability studies showed that irrespective of preparative technique and storage conditions all samples showed at least partial reversion to the crystalline state after storage. Quench cooling of drug melts may be of use as a preparative technique however it can result in chemical degradation. Ball milling may also be of use as a preparative technique however its effectiveness is dependent on the unit cell structure of the compound.

Microfluidic-based devices have allowed miniaturization and increased parallelism of many common functions in biological assays; however, development of a practical technology for microfluidic-based fluorescence-activated cell sorting has proved challenging. Although a variety of different physical on-chip switch mechanisms have been proposed, none has satisfied simultaneously the requirements of high throughput, purity, and recovery of live, unstressed mammalian cells. Here we show that optical forces can be used for the rapid (2-4 ms), active control of cell routing on a microfluidic chip. Optical switch controls reduce the complexity of the chip and simplify connectivity. Using all-optical switching, we have implemented a fluorescence-activated microfluidic cell sorter and evaluated its performance on live, stably transfected HeLa cells expressing a fused histone-green fluorescent protein. Recovered populations were verified to be both viable and unstressed by evaluation of the transcriptional expression of two genes, HSPA6 and FOS, known indicators of cellular stress.

To facilitate quantitation of cellular apoptotic responses to various antineoplastic agents, a laser-based technology, Optophoresis, has been developed to provide analysis of cells without any need for labeling or cell processing. Optophoresis is defined as the analysis of the motion of cells, where the motion is either induced or modified by a moving optical gradient field, which produces radiation pressure forces on the cells in an aqueous suspension. Quantitation of the induced motion provides a basis for distinguishing one population of cells from another. One Optophoretic technique, Fast Scan, measures the distribution of distances traversed by a population of cells when exposed to a fast-moving optical gradient. Fast Scan was validated using a cell-based model of chronic myeloid leukemia treated with Gleevec, a specific inhibitor of aberrant Bcr-Abl protein kinase. The Optophoretic measurements were quantitatively comparable to reference assays with regard to drug selectivity and potency and to target specificity, demonstrating the suitability of this technology for pharmaceutical and clinical applications.

The change in the resistivity in a Co nanowire due to the anisotropic magnetoresistivity effect is investigated using the finite element method. The wire has a square cross-section of 200×200 nm 2 . We compare our results with experimental investigations. The numerical results show reduction of the resistivity during hysteresis. Magnetoresistance (MR) decreases gradually until the coercive field is reached and then jumps back to the initial value. If we move the electrodes into the centre of the nanowire the MR effect is reduced because we neglect the formed domains at the end of the nanowire.

A method to determine the minimum energy path between two stable states in a magnetic system is used to investigate magnetic reversal of an irregularly shaped columnar grain. The method describes the magnetization reversal process initiated by thermal excitations in zero applied field or fields below the intrinsic switching field. In addition to the energy barrier, an effective volume V eff is calculated as a function of material exchange interaction, uniaxial crystalline anisotropy, and particle length. The minimum energy barrier paths follow that of intrinsic switching where with decreasing exchange the reversal modes go from uniform rotation to end nucleation and subsequent expansion to reversal by vortex excitation. The effective reversal volume decreases with decreasing exchange and increasing crystalline anisotropy. Decreasing the particle length also decreases the effective volume once the length becomes less than the excitation length. A very simple analytic wall model nicely indicates these trends. Analysis of measured thermal reversal fields for CrO 2 and Fe explain the inferred effective volumes in these particles.

A parallel finite element micromagnetics package has been implemented, that is highly scalable, easily portable and combines different solvers for the micromagnetic equations. The implementation is based on the standard Galerkin discretization on tetrahedral meshes with linear basis functions. A static energy minimization, a dynamic time integration, and the nudged elastic band method have been implemented. The details of the implementation and some aspects of the optimization are discussed and timing and speedup results are given. Nucleation and magnetization reversal processes in permalloy nanodots are investigated with this micromagnetics package.

Separation of simulants of biological warfare agents from blood using dielectrophoresis (DEP) was demonstrated in a miniaturized DEP device. The device was fabricated by laminating five different layers (all 40 mm×40 mm) including a polycarbonate substrate, a pressure sensitive acrylic adhesive (PSA) layer, a patterned polyimide layer with a flip-chip bonded dielectrophoresis chip (DEP chip), a PSA layer with microfluidic channel, and a glass cover plate. The DEP chip consisted of repetitive interdigitated electrodes with characteristic dimension of 50 μm. This device was employed to separate different simulants of biological warfare agents (BWA), namely Bacillus cereus (B. cereus), Escherichia coli (E. coli) and Listeria monocytogenes (L. monocytogenes), from blood, individually or simultaneously. PCR amplification, which was inhibited by blood components in pre-separation samples, successfully revealed bands in post-separation samples containing single or multiple BWA. Up to 97% efficiency of separation was achieved as demonstrated by culturing post-separation E. coli cells. The DEP device described here can potentially be used to reduce sample complexity for detection of infectious disease pathogens and biological warfare agents.

The clinical lifetime of poly(methyl methacrylate) (PMMA) bone cement is considerably longer than the time over which it is convenient to perform creep testing. Consequently, it is desirable to be able to predict the long term creep behavior of bone cement from the results of short term testing. A simple method is described for prediction of long term creep using the principle of time-temperature equivalence in polymers. The use of the method is illustrated using a commercial acrylic bone cement. A creep strain of approximately 0.6% is predicted after 400 days under a constant flexural stress of 2 MPa. The temperature range and stress levels over which it is appropriate to perform testing are described. Finally, the effects of physical aging on the accuracy of the method are discussed and creep data from aged cement are reported.

Microelectronic arrays have been developed for DNA hybridization analysis of point mutations, single nucleotide polymorphisms, short tandem repeats and gene expression. In addition to a variety of molecular biology and genomic research applications, such devices will also be used for infectious disease detection, genetic and cancer diagnostics, and pharmacogenomic applications. These microelectronic array devices are able to produce defined electric fields on their surfaces that allow charged molecules and other entities to be transported to or from any test site or micro-location on the planar surface of the device. These molecules and entities include DNA, RNA, proteins, enzymes, antibodies and cells. Electronic-based molecule addressing and hybridization can then be carried out, where the electric field is now used to greatly accelerate the hybridization reactions that occur on the selected test sites. When reversed, the electric field can be used to provide an additional parameter for improved hybridization. Special low-conductance buffers have been developed that provide for the rapid transport of the DNA molecules and facilitate the electronic hybridization reactions under conditions that do not support hybridization. Important to the device function is the permeation layer that overcoats the underlying microelectrodes. Generally composed of a porous hydrogel material impregnated with attachment chemistry, this permeation layer prevents the destruction of analytes at the active microelectrode surface, ameliorates the adverse effects of electrolysis products on the sensitive hybridization and affinity reactions, and serves as a support structure for attaching DNA probes and other molecules to the array. The microelectronic chip or array device is incorporated into a cartridge package (NanoChip trade mark cartridge) that provides the electronic, optical, and fluidic interfacing. A complete instrument system (NanoChip trade mark Molecular Biology Workstation) provides a chip loader, fluorescent reader, computer control interface and data display screen. The probe loader component allows DNA probes or target molecules (polymerase chain reactions amplicons, genomic DNA, RNA, etc.) to be selectively addressed to the array test sites, providing the end-user with 'make your own chip' capabilities. The electronic hybridization can then be carried out and the chip analyzed using a fluorescent detector system. In addition to carrying out rapid, accurate and highly reliable genotyping (point mutations, single nucleotide polymorphisms, short tandem repeats), other future applications include gene expression analysis, or on-chip amplification, immunoassays and cell separation and selection. Smaller and more compact systems are also being designed for portable sample to answer and point of care diagnostics.