An attenuated Salmonella enterica serovar Typhimurium strain lacking the ZnuABC transporter induces protection in a mouse intestinal model of Salmonella infection

Salmonella enterica serovar Typhimurium has long been recognised as a zoonotic pathogen of economic significance in animals and humans. Attempts to protect humans and livestock may be based on immunization with vaccines aimed to induce a protective response. We recently demonstrated that the oral administration of a Salmonella enterica serovar Typhimurium strain unable to synthesize the zinc transporter ZnuABC is able to protect mice against systemic salmonellosis induced by a virulent homologous challenge. This finding suggested that this mutant strain could represent an interesting candidate vaccine for mucosal delivery. In this study, the protective effect of this Salmonella strain was tested in a streptomycin-pretreated mouse model of salmonellosis that is distinguished by the capability of evoking typhlitis and colitis. The here reported results demonstrate that mice immunized with Salmonella enterica serovar Typhimurium (S. Typhimurium) SA186 survive to the intestinal challenge and, compared to control mice, show a reduced number of virulent bacteria in the gut, with milder signs of inflammation. This study demonstrates that the oral administration a of S. Typhimurium strain lacking ZnuABC is able to elicit an effective immune response which protects mice against intestinal S. Typhimurium infection. These results, collectively, suggest that the streptomycin-pretreated mouse model of S. typhimurium infection can represent a valuable tool to screen S. typhimurium attenuated mutant strains and potentially help to assess their protective efficacy as potential live vaccines.

The Supreme Court Confirmation Process and Its Implications

In recent history, there has been a trend of increasing partisan polarization throughout most of the American political system. Some of the impacts of this polarization are obvious; however, there is reason to believe that we miss some of the indirect effects of polarization. Accompanying the trend of increased polarization has been an increase in the contentiousness of the Supreme Court confirmation process. I believe that these two trends are related. Furthermore, I argue that these trends have an impact on judicial behavior. This is an issue worth exploring, since the Supreme Court is the most isolated branch of the federal government. The Constitution structured the Supreme Court to ensure that it was as isolated as possible from short-term political pressures and interests. This study attempts to show how it may be possible that those goals are no longer being fully achieved. My first hypothesis in this study is that increases in partisan polarization are a direct cause of the increase in the level of contention during the confirmation process. I then hypothesize that the more contention a justice faces during his or her confirmation process, the more ideologically extreme that justice will then vote on the bench. This means that a nominee appointed by a Republican president will tend to vote even more conservatively than was anticipated following a contentious confirmation process, and vice versa for Democratic appointees. In order to test these hypotheses, I developed a data set for every Supreme Court nominee dating back to President Franklin D. Roosevelt¿s appointments (1937). With this data set, I ran a series of regression models to analyze these relationships. Statistically speaking, the results support my first hypothesis in a fairly robust manner. My regression results for my second hypothesis indicate that the trend I am looking for is present for Republican nominees. For Democratic nominees, the impacts are less robust. Nonetheless, as the results will show, contention during the confirmation process does seem to have some impact on judicial behavior. Following my quantitative analysis, I analyze a series of case studies. These case studies serve to provide tangible examples of these statistical trends as well as to explore what else may be going on during the confirmation process and subsequent judicial decision-making. I use Justices Stevens, Rehnquist, and Alito as the subjects for these case studies. These cases will show that the trends described above do seem to be identifiable at the level of an individual case. These studies further help to indicate other potential impacts on judicial behavior. For example, following Justice Rehnquist¿s move from Associate to Chief Justice, we see a marked change in his behavior. Overall, this study serves as a means of analyzing some of the more indirect impacts of partisan polarization in modern politics. Further, the study offers a means of exploring some of the possible constraints (both conscious and subconscious) that Supreme Court justices may feel while they decide how to cast a vote in a particular case. Given the wide-reaching implications of Supreme Court decisions, it is important to try to grasp a full view of how these decisions are made.

Neuro-imaging of cerebral ischemic stroke

Major progress has recently been made in the neuro-imaging of stroke as a result of improvements in imaging hardware and software. Imaging may be based on either magnetic resonance imaging (MRI) or computed tomography (CT) techniques. Imaging should provide information on the entire vascular cervical and intracranial network, from the aortic arch to the circle of Willis. Equally, it should also give information on the viability of brain tissue and brain hemodynamics. CT has the advantage in the detection of acute hemorrhage whereas MRI offers more accurate pathophysiological information in the follow-up of patients.

[Irritation of the iliopsoas tendon after total hip arthroplasty]

Chronic irritation of the iliopsoas tendon is a rare cause of persistent pain after total joint replacement of the hip. In the majority of cases, pain results from a mechanical conflict between the iliopsoas tendon and the anterior edge of the acetabular cup after total hip arthroplasty. Pain can be reproduced by active flexion of the hip and by active raising of the straightened leg. In addition, painful leg raising against resistance and passive hyperextension are suggestive of an irritation of the iliopsoas tendon. Symptoms evolve from a mechanical irritation of the iliopsoas tendon and an oversized or retroverted acetabular cup, screws penetrating into the inner aspect of the ilium, or from bone cement protruding beyond the anterior acetabular rim. The diagnosis may be assumed on conventional radiographs and confirmed by CT scans. Fifteen patients with psoas irritation after total hip replacement are reported on. Eleven patients were treated surgically. The acetabular cup was revised and reoriented with more anteversion in six patients, isolated screws penetrating into the tendon were cut and leveled in three patients, and prominent bone cement in conflict with the tendon was resected once. A partial release of the iliopsoas tendon only was performed in another patient. Follow-up examination (range: 11-89 months) revealed that nine patients were free of pain and two patient had mild residual complaints. Psoas irritation in combination with total hip replacement can be prevented by a correct surgical technique, especially with proper selection of the cup size and insertion of the acetabular cup avoiding a rim position exceeding the level of the anterior acetabular rim.

Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism

BACKGROUND: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become an established screening method for the diagnosis of primary aldosteronism. Plasma renin activity (PRA) is usually measured to define ARR although, increasingly, renin concentration alone is often measured in clinical routine. OBJECTIVE: To determine the threshold of ARR using active renin concentration to screen for primary aldosteronism. DESIGN AND PARTICIPANTS: To determine the ARR threshold based on plasma immunoreactive renin concentration (irR), we measured plasma aldosterone concentration (PAC), irR and PRA in 36 hypertensive patients, nine thereof with adrenal adenoma, and compared ARRs calculated from irR and PRA, respectively. SETTING: Single-centre, hypertension clinic in a tertiary care hospital. RESULTS: PRA ranged from 0.41-14.9 ng/ml per h and irR from 1.1-72 ng/l. There was an excellent correlation between PRA and irR (r = 0.98, P < 0.0001) and between ARRPRA and ARRirR (r = 0.96, P < 0.0001). An ARRPRA > 750 pmol/l per ng/ml per h was previously found to be highly predictive of primary aldosteronism because 90% of the corresponding patients failed to suppress PAC upon saline infusion or fludrocortisone. The corresponding threshold value for ARRirR was 150 pmol/ng in our patients. Using these cut-offs, nine subjects had both increased ARRPRA and ARRirR while, in three patients, either ARRPRA or ARRirR were increased. The nine patients with increased ARRPRA and ARRirR also had PAC > 650 pmol/l. Only these patients had adrenal adenomas. CONCLUSIONS: The ARR threshold to screen for primary aldosteronism may be based on measurement of irR. An ARRirR > 150 pmol/ng may indicate primary aldosteronism.

A new method to monitor visual field defects caused by photoreceptor degeneration by quantitative optical coherence tomography

PURPOSE: To correlate the dimension of the visual field (VF) tested by Goldman kinetic perimetry with the extent of visibility of the highly reflective layer between inner and outer segments of photoreceptors (IOS) seen in optical coherence tomography (OCT) images in patients with retinitis pigmentosa (RP). METHODS: In a retrospectively designed cross-sectional study, 18 eyes of 18 patients with RP were examined with OCT and Goldmann perimetry using test target I4e and compared with 18 eyes of 18 control subjects. A-scans of raw scan data of Stratus OCT images (Carl Zeiss Meditec, AG, Oberkochen, Germany) were quantitatively analyzed for the presence of the signal generated by the highly reflective layer between the IOS in OCT images. Starting in the fovea, the distance to which this signal was detectable was measured. Visual fields were analyzed by measuring the distance from the center point to isopter I4e. OCT and visual field data were analyzed in a clockwise fashion every 30 degrees , and corresponding measures were correlated. RESULTS: In corresponding alignments, the distance from the center point to isopter I4e and the distance to which the highly reflective signal from the IOS can be detected correlate significantly (r = 0.75, P < 0.0001). The greater the distance in VF, the greater the distance measured in OCT. CONCLUSIONS: The authors hypothesize that the retinal structure from which the highly reflective layer between the IOS emanates is of critical importance for visual and photoreceptor function. Further research is warranted to determine whether this may be useful as an objective marker of progression of retinal degeneration in patients with RP.

Driver Safety in Far-side and Far-oblique Crashes: A Study of Patrol Vehicles in the United States of America

The dissertation titled "Driver Safety in Far-side and Far-oblique Crashes" presents a novel approach to assessing vehicle cockpit safety by integrating Human Factors and Applied Mechanics. The methodology of this approach is aimed at improving safety in compact mobile workspaces such as patrol vehicle cockpits. A statistical analysis performed using Michigan state's traffic crash data to assess various contributing factors that affect the risk of severe driver injuries showed that the risk was greater for unrestrained drivers (OR=3.38, p<0.0001) and for incidents involving front and far-side crashes without seatbelts (OR=8.0 and 23.0 respectively, p<0.005). Statistics also showed that near-side and far-side crashes pose similar threat to driver injury severity. A Human Factor survey was conducted to assess various Human-Machine/Human-Computer Interaction aspects in patrol vehicle cockpits. Results showed that tasks requiring manual operation, especially the usage of laptop, would require more attention and potentially cause more distraction. A vehicle survey conducted to evaluate ergonomics-related issues revealed that some of the equipment was in airbag deployment zones. In addition, experiments were conducted to assess the effects on driver distraction caused by changing the position of in-car accessories. A driving simulator study was conducted to mimic HMI/HCI in a patrol vehicle cockpit (20 subjects, average driving experience = 5.35 years, s.d. = 1.8). It was found that the mounting locations of manual tasks did not result in a significant change in response times. Visual displays resulted in response times less than 1.5sec. It can also be concluded that the manual task was equally distracting regardless of mounting positions (average response time was 15 secs). Average speeds and lane deviations did not show any significant results. Data from 13 full-scale sled tests conducted to simulate far-side impacts at 70 PDOF and 40 PDOF was used to analyze head injuries and HIC/AIS values. It was found that accelerations generated by the vehicle deceleration alone were high enough to cause AIS 3 - AIS 6 injuries. Pretensioners could mitigated injuries only in 40 PDOF (oblique) impacts but are useless in 70 PDOF impacts. Seat belts were ineffective in protecting the driver's head from injuries. Head would come in contact with the laptop during a far-oblique (40 PDOF) crash and far-side door for an angle-type crash (70 PDOF). Finite Element analysis head-laptop impact interaction showed that the contact velocity was the most crucial factor in causing a severe (and potentially fatal) head injury. Results indicate that no equipment may be mounted in driver trajectory envelopes. A very narrow band of space is left in patrol vehicles for installation of manual-task equipment to be both safe and ergonomic. In case of a contact, the material stiffness and damping properties play a very significant role in determining the injury outcome. Future work may be done on improving the interiors' material properties to better absorb and dissipate kinetic energy of the head. The design of seat belts and pretensioners may also be seen as an essential aspect to be further improved.

The Effect of Cobalt Upon Current Efficiency in the Electrolysis of Zinc Sulphate Solutions

The detrimental effect of the presence of cobalt upon the current efficiency, in the commercial production of zinc by electrolysis, has been recognized for some time. Most authorities differ upon the maximum amount of cobalt allowable. This is due to the fact that the presence of other impurities either increases or diminishes the detrimental effects of the cobalt. The following tests were made with the object in view of ascertaining the relation, if any, between the amount of cobalt present and the current efficiency during the electrolysis of an otherwise pure zinc sulfate solution. The results obtained from these observations indicate that there is little apparent relation between the cobalt concentration of a given solution of zinc sulfate and the current efficiency that may be obtained on the electrolysis of that solution. For certain cobalt concentrations, however, it was noted that the time factor played an important part.

Genetic and phenotypic diversity in selected genotypes of tef [Eragrostis tef (Zucc.)] Trotter

Tef [Eragrostis tef (Zucc.) Trotter] is an important staple food crop, especially in Ethiopia where it is annually grown on 2.8 million hectares of land. It is important for food security in the region, in spite of having a low yield, mainly due to lodging. In this study, 15 representative landraces as well as three improved varieties have been selected for in-depth characterization of many parameters, especially those implicated in yield. The genotypes were clustered into six groups, mainly based on agronomic traits and about 80% of the diversity in the genotypes could be explained on the basis of four principal components. In general, all traits investigated showed substantial diversity among genotypes, offering high chances for improving tef through direct selection or intra-specific hybridization. Moreover, in view of climatic changes, breeding with early maturing landraces such as Red dabi or Karadebi would be advantageous to cope with moisture scarcity during the later stage of crop maturity.

Ankle joint pressure changes in a pes cavovarus model: supramalleolar valgus osteotomy versus lateralizing calcaneal osteotomy

BACKGROUND: A fixed cavovarus foot deformity can be associated with anteromedial ankle arthrosis due to elevated medial joint contact stresses. Supramalleolar valgus osteotomies (SMOT) and lateralizing calcaneal osteotomies (LCOT) are commonly used to treat symptoms by redistributing joint contact forces. In a cavovarus model, the effects of SMOT and LCOT on the lateralization of the center of force (COF) and reduction of the peak pressure in the ankle joint were compared. METHODS: A previously published cavovarus model with fixed hindfoot varus was simulated in 10 cadaver specimens. Closing wedge supramalleolar valgus osteotomies 3 cm above the ankle joint level (6 and 11 degrees) and lateral sliding calcaneal osteotomies (5 and 10 mm displacement) were analyzed at 300 N axial static load (half body weight). The COF migration and peak pressure decrease in the ankle were recorded using high-resolution TekScan pressure sensors. RESULTS: A significant lateral COF shift was observed for each osteotomy: 2.1 mm for the 6 degrees (P = .014) and 2.3 mm for the 11 degrees SMOT (P = .010). The 5 mm LCOT led to a lateral shift of 2.0 mm (P = .042) and the 10 mm LCOT to a shift of 3.0 mm (P = .006). Comparing the different osteotomies among themselves no significant differences were recorded. No significant anteroposterior COF shift was seen. A significant peak pressure reduction was recorded for each osteotomy: The SMOT led to a reduction of 29% (P = .033) for the 6 degrees and 47% (P = .003) for the 11 degrees osteotomy, and the LCOT to a reduction of 41% (P = .003) for the 5 mm and 49% (P = .002) for the 10 mm osteotomy. Similar to the COF lateralization no significant differences between the osteotomies were seen. CONCLUSION: LCOT and SMOT significantly reduced anteromedial ankle joint contact stresses in this cavovarus model. The unloading effects of both osteotomies were equivalent. More correction did not lead to significantly more lateralization of the COF or more reduction of peak pressure but a trend was seen. CLINICAL RELEVANCE: In patients with fixed cavovarus feet, both SMOT and LCOT provided equally good redistribution of elevated ankle joint contact forces. Increasing the amount of displacement did not seem to equally improve the joint pressures. The site of osteotomy could therefore be chosen on the basis of surgeon's preference, simplicity, or local factors in case of more complex reconstructions.

Solutions to the Chronological Puzzles in Book 1 of the Chronicle of Matthew of Edessa

The chronological inconsistency in the first book of Matthew of Edessa's Chronicle is well-known. Some of his are dates accurate to the day, while others err by up to 50 years, with no immediately apparent pattern of error. In this talk I will examine some of these chronological puzzles, by untangling the five main themes that run through the book. By demonstrating how these chronological errors may have arisen, and why certain events in the chronicle are dated much more accurately than others, light may be shed on the sources and methodologies that Matthew used to compose his chronicle.

The Family Preservation Philosophy and Therapy With Lesbian Clients

Family preservation is generally viewed in terms of a rather narrow practice definition. However, it's underlying philosophy offers a strong framework for building a positive, nonbiased helping alliance with lesbian clients in a therapeutic setting. The family preservation philosophy offers a unique heuristic for helping professionals to work with lesbians. Family preservation values teach that the therapist must start with the client's reality, recognize the particular needs of that client, and use the client's strengths in treatment. Also inherent in this perspective is respect and sensitivity to the lesbian client's "cultural context, experience, and history" (Family Preservation Institute, 1995). In other words, in the family preservation philosophy there is no assumption of heterosexuality in the therapeutic relationship; rather there is an assumption of unconditional positive regard. Further, clients are engaged in a dialogue and encouraged to name the challenges they encounter in their own words, from their own perspective. All of these principles will help empower lesbian clients. Lesbians may avoid traditional mental health services in times of need, preferring to depend on alternative services or friendship support networks. The choice not to seek help through mainstream agencies may be based on previous negative experience or on an assumption of the homophobic attitudes which are often inherent in such services. Traditional services are usually based on the medical model. Services based on the family preservation philosophy, however, have the capability of creating therapeutic relationships in which there is no assumption of heterosexuality, where the lesbian client is respected and viewed as a whole, healthy individual.

cDNA cloning and expression of a novel cell surface-expressed \b heparan sulfate/heparin \b interacting \b protein (HIP) from human cell lines and functional studies of a synthetic HIP peptide

Heparan sulfate proteoglycans and their corresponding binding sites have been suggested to play an important role during the initial attachment of blastocysts to uterine epithelium and human trophoblastic cell lines to uterine epithelial cell lines. Previous studies on RL95 cells, a human uterine epithelial cell line, characterized a single class of cell surface heparin/heparan sulfate (HP/HS)-binding sites. Three major HP/HS-binding peptide fragments were isolated from RL95 cell surfaces by tryptic digestion and partial amino-terminal amino acid sequence from each peptide fragment was obtained. In the current study, using the approaches of reverse transcription-polymerase chain reaction and cDNA library screening, a novel cell surface $\rm\underline{H}$P/HS $\rm\underline{i}$nteracting $\rm\underline{p}$rotein (HIP) has been isolated from RL95 cells. The full-length cDNA of HIP encodes a protein of 259 amino acids with a calculated molecular weight of 17,754 Da and pI of 11.75. Transfection of HIP cDNA into NIH-3T3 cells demonstrated cell surface expression and a size similar to that of HIP expressed by human cells. Predicted amino acid sequence indicates that HIP lacks a membrane spanning region and has no consensus sites for glycosylation. Northern blot analysis detected a single transcript of 1.3 kb in both total RNA and poly(A$\sp+$) RNA. Examination of human cell lines and normal tissues using both Northern blot and Western blot analysis revealed that HIP is differentially expressed in a variety of human cell lines and normal tissues, but absent in some cell lines examined. HIP has about 80% homology, at the level of both mRNA and protein, to a rodent protein, designated as ribosomal protein L29. Thus, members of the L29 family may be displayed on cell surfaces where they participate in HP/HS binding events. Studies on a synthetic peptide derived from HIP demonstrate that HIP peptide binds HS/HP with high selectivity and has high affinity (Kd = 10 nM) for a subset of polysaccharides found in commercial HIP preparations. Moreover, HIP peptide also binds certain forms of cell surface, but not secreted or intracellular. HS expressed by RL95 and JAR cells. This peptide supports the attachment of several human trophoblastic cell lines and a variety of mammalian adherent cell lines in a HS-dependent fashion. Furthermore, studies on the subset of HP specifically recognized by HIP peptide indicate that this high-affinity HP (HA-HP) has a larger median MW and a greater negative charge density than bulk HP. The minimum size of oligosaccharide required to bind to HIP peptide with high affinity is a septa- or octasaccharide. HA-HP also quantitatively binds to antithrombin-III (AT-III) with high affinity, indicating that HIP peptide and AT-III may recognize the same or similar oligosaccharide structure(s). Furthermore, HIP peptide antagonizes HP action and promotes blood coagulation in both factor Xa- and thrombin-dependent assays. Finally, HA-HP recognized by HP peptide is highly enriched with anticoagulant activity relative to bulk HP. Collectively, these results demonstrate that HIP may play a role in the HP/HS-involved cell-cell and cell-matrix interactions and recognizes a motif in HP similar or identical to that recognized by AT-III and therefore, may modulate blood coagulation. ^

Essentials of forensic post-mortem MR imaging in adults

Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system.

Factorial designs: an overview with applications to orthodontic clinical trials.

Factorial designs for clinical trials are often encountered in medical, dental, and orthodontic research. Factorial designs assess two or more interventions simultaneously and the main advantage of this design is its efficiency in terms of sample size as more than one intervention may be assessed on the same participants. However, the factorial design is efficient only under the assumption of no interaction (no effect modification) between the treatments under investigation and, therefore, this should be considered at the design stage. Conversely, the factorial study design may also be used for the purpose of detecting an interaction between two interventions if the study is powered accordingly. However, a factorial design powered to detect an interaction has no advantage in terms of the required sample size compared to a multi-arm parallel trial for assessing more than one intervention. It is the purpose of this article to highlight the methodological issues that should be considered when planning, analysing, and reporting the simplest form of this design, which is the 2 × 2 factorial design. An example from the field of orthodontics using two parameters (bracket type and wire type) on maxillary incisor torque loss will be utilized in order to explain the design requirements, the advantages and disadvantages of this design, and its application in orthodontic research.