The effect of antiretroviral treatment of different durations in primary HIV infection.

OBJECTIVES: To compare immunological, virological and clinical outcomes in persons initiating combination antiretroviral therapy (cART of different durations within 6 months of seroconversion (early treated) with those who deferred therapy (deferred group). DESIGN: CD4 cell and HIV-RNA measurements for 'early treated' individuals following treatment cessation were compared with the corresponding ART-free period for the 'deferred' group using piecewise linear mixed models. Individuals identified during primary HIV infection were included if they seroconverted from 1st January 1996 and were at least 15 years of age at seroconversion. Those with at least 2 CD4 less than 350 cells/microl or AIDS within the first 6 months following seroconversion were excluded. RESULTS: Of 348 'early treated' patients, 147 stopped cART following treatment for at least 6 (n = 38), more than 6-12 (n = 40) or more than 12 months (n = 69). CD4 cell loss was steeper for the first 6 months following cART cessation, but subsequent loss rate was similar to the 'deferred' group (n = 675, P = 0.26). Although those treated for more than 12 months appeared to maintain higher CD4 cell counts following cART cessation, those treated for 12 months or less had CD4 cell counts 6 months after cessation comparable to those in the 'deferred' group. There was no difference in HIV-RNA set points between the 'early' and 'deferred' groups (P = 0.57). AIDS rates were similar but death rates, mainly due to non-AIDS causes, were higher in the 'deferred' group (P = 0.05). CONCLUSION: Transient cART, initiated within 6 months of seroconversion, seems to have no effect on viral load set point and limited beneficial effect on CD4 cell levels in individuals treated for more than 12 months. Its long-term effects remain inconclusive and need further investigation.

The SYNTAX score predicts early mortality risk in the elderly with acute coronary syndrome having primary PCI.

BACKGROUND: The SYNTAX score (SXscore), an angiographic score reflecting coronary lesion complexity, predicts clinical outcomes in patients with left main or multivessel disease, and in patients with ST-segment elevation myocardial infarction undergoing primary PCI. The clinical SXscore (CSS) integrates the SXscore and clinical variables (age, ejection fraction, serum creatinine) into a single score. We analyzed these scores in elderly patients with acute coronary syndrome (ACS) undergoing primary PCI. The purpose of this analysis was not to decide which patients should undergo PCI, but to predict clinical outcomes in this population. METHODS: The SXscore was determined in a consecutive series of 114 elderly patients (mean age, 79.6 ± 4.1 years) undergoing primary PCI for ACS. Outcomes were stratified according to SXscore tertiles: SXLOW ≤15 (n = 39), 15< SXMID <23 (n = 40), and SXHIGH ≥23 (n = 35). The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were nonfatal major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and 1-year outcomes in patients discharged alive. RESULTS: Mortality at 30 days was higher in the SXHIGH group compared with the aggregate SXLOW+MID group (37.1% vs 5.1%; P<.0001), and in the CSSHIGH group compared with the aggregate CSSLOW+MID group (25.5% vs 1.4%; P=.0001). MACCE rates at 30 days were similar among SXscore tertiles. The CSS predicted 1-year MACCE rates (12.1% for CSSHIGH vs 3.1% for CSSLOW+MID; P=.03). CONCLUSIONS: The SXscore predicts 30-day mortality in elderly patients with ACS undergoing primary PCI. In patients discharged alive, the CSS predicts risk of MACCE at 1 year.

Iowa Drivers Manual

The rules and regulations for operating a motered vechicle in Iowa

Drivers License Cost Study Report, 2003

Drivers License Cost Study Report

Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.

BACKGROUND: Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. METHODS: MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. RESULTS: Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004). CONCLUSIONS: Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin-transmission vs sporadic appearance-of these variants determines their impact on ART needs to be further explored.

Suboptimal access to primary healthcare among street-based sex workers in southwest Switzerland.

OBJECTIVES: Street-based sex workers (SSWs) in Lausanne, Switzerland, are poorly characterised. We set out to quantify potential vulnerability factors in this population and to examine SSW healthcare use and unmet healthcare requirements. METHODS: We conducted a cross-sectional questionnaire-based survey among SSWs working in Lausanne's red light district between 1 February and 31 July 2010, examining SSW socio-demographic characteristics and factors related to their healthcare. RESULTS: We interviewed 50 SSWs (76% of those approached). A fifth conducted their interviews in French, the official language in Lausanne. 48 participants (96%) were migrants, of whom 33/48 (69%) held no residence permit. 22/50 (44%) had been educated beyond obligatory schooling. 28/50 (56%) had no health insurance. 18/50 (36%) had been victims of physical violence. While 36/50 (72%) had seen a doctor during the preceding 12 months, only 15/50 (30%) were aware of a free clinic for individuals without health insurance. Those unaware of free services consulted emergency departments or doctors outside Switzerland. Gynaecology, primary healthcare and dental services were most often listed as needed. Two individuals (of 50, 4%) disclosed positive HIV status; of the others, 24/48 (50%) had never had an HIV test. CONCLUSIONS: This vulnerable population comprises SSWs who, whether through mobility, insufficient education or language barriers, are unaware of services they are entitled to. With half the participants reporting no HIV testing, there is a need to enhance awareness of available facilities as well as to increase provision and uptake of HIV testing.

Several neuronal and axonal types form long intrinsic connections in the cat primary auditory cortical field (AI).

Intrinsic connections in the cat primary auditory field (AI) as revealed by injections of Phaseolus vulgaris leucoagglutinin (PHA-L) or biocytin, had an anisotropic and patchy distribution. Neurons, labelled retrogradely with PHA-L were concentrated along a dorsoventral stripe through the injection site and rostral to it; the spread of rostrally located neurons was greater after injections into regions of low rather than high characteristic frequencies. The intensity of retrograde labelling varied from weak and granular to very strong and Golgi-like. Out of 313 Golgi like retrogradely labelled neurons 79.6% were pyramidal, 17.2% multipolar, 2.6% bipolar, and 0.6% bitufted; 13.4% were putatively inhibitory, i.e. aspiny or sparsely spiny multipolar, or bitufted. Individual anterogradely labelled intrinsic axons were reconstructed for distances of 2 to 7 mm. Five main types were distinguished on the basis of the branching pattern and the location of synaptic specialisations. Type 1 axons travelled horizontally within layers II to VI and sent collaterals at regular intervals; boutons were only present in the terminal arborizations of these collaterals. Type 2 axons also travelled horizontally within layers II to VI and had rather short and thin collateral branches; boutons or spine-like protrusions occurred in most parts of the axon. Type 3 axons travelled obliquely through the cortex and formed a single terminal arborization, the only site where boutons were found. Type 4 axons travelled for some distance in layer I; they formed a heterogeneous group as to their collaterals and synaptic specializations. Type 5 axons travelled at the interface between layer VI and the white matter; boutons en passant, spine-like protrusions, and thin short branches with boutons en passant were frequent all along their trajectory. Thus, only some axonal types sustain the patchy pattern of intrinsic connectivity, whereas others are involved in a more diffuse connectivity.

Airline Consolidation and the Distribution of Traffic between Primary and Secondary Hubs

Several airline consolidation events have recently been completed both in Europe and in the United States. The model we develop considers two airlines operating hub-and-spoke networks, using different hubs to connect the same spoke airports. We assume the airlines to be vertically differentiated, which allows us to distinguish between primary and secondary hubs. We conclude that this differentiation in air services becomes more accentuated after consolidation, with an increased number of flights being channeled through the primary hub. However, congestion can act as a brake on the concentration of flight frequency in the primary hub following consolidation. Our empirical application involves an analysis of Delta s network following its merger with Northwest. We find evidence consistent with an increase in the importance of Delta s primary hubs at the expense of its secondary airports. We also find some evidence suggesting that the carrier chooses to divert traffic away from those hub airports that were more prone to delays prior to the merger, in particular New York s JFK airport. Keywords: primary hub; secondary hub; airport congestion; airline consolidation; airline networks JEL Classi fication Numbers: D43; L13; L40; L93; R4

The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network.

PURPOSE: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

Canine distemper virus infection of primary hippocampal cells induces increase in extracellular glutamate and neurodegeneration.

The canine distemper virus (CDV) belongs to the Morbillivirus genus which includes important human pathogens like the closely related measles virus. CDV infection can reach the nervous system where it causes serious malfunctions. Although this pathology is well described, the molecular events in brain infection are still poorly understood. Here we studied infection in vitro by CDV using a model of dissociated cell cultures from newborn rat hippocampus. We used a recombinant CDV closely related to the neurovirulent A75/17 which also expresses the enhanced green fluorescent protein. We found that infected neurons and astrocytes could be clearly detected, and that infection spreads only slowly to neighboring cells. Interestingly, this infection causes a massive cell death of neurons, which includes also non-infected neurons. Antagonists of NMDA-type or alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA)-type glutamate receptors could slow down this neuron loss, indicating an involvement of the glutamatergic system in the induction of cell death in infected and non-infected cells. Finally, we show that, following CDV infection, there is a steady increase in extracellular glutamate in infected cultures. These results indicate that CDV infection induces excitotoxic insults on neurons via glutamatergic signaling.

Paved Shoulders on Primary Highways in Iowa: An Analysis of Shoulder Surfacing Criteria, Costs, and Benefits, 2001

The value of providing paved shoulders adjacent to many higher volume roadways has been accepted in many states across the country. Iowa’s paved shoulder policy is considerably more conservative than neighboring states, particularly on rural four-lane and high-volume two-lane highways. The objectives of this research are to examine current design criteria for shoulders employed in Iowa and surrounding states, compare benefits and costs of alternative surface types and widths, and make recommendations based on this analysis for consideration in future design policies for primary highway in Iowa. The report finds that many safety and maintenance benefits would result from enhancing Iowa’s paved shoulder and rumble strip design practices for freeways, expressways, and Super 2 highway corridors. The benefits of paved shoulders include reduced numbers of certain crashes, higher capacity potentials, reduced maintenance, enhanced opportunities for other users such as bicyclists, and even possible increased longevity of pavements. Alternative paved shoulder policies and programming strategies are also offered, with detailed assessments of the benefits, costs, and budget impacts.

Comparisons of preoperative three-dimensional planning and surgical reconstruction in primary cementless total hip arthroplasty.

Reconstruction of important parameters such as femoral offset and torsion is inaccurate, when templating is based on plain x-rays. We evaluate intraoperative reproducibility of pre-operative CT-based 3D-templating in a consecutive series of 50 patients undergoing primary cementless THA through an anterior approach. Pre-operative planning was compared to a postoperative CT scan by image fusion. The implant size was correctly predicted in 100% of the stems, 94% of the cups and 88% of the heads (length). The difference between the planned and the postoperative leg length was 0.3 + 2.3 mm. Values for overall offset, femoral anteversion, cup inclination and anteversion were 1.4 mm ± 3.1, 0.6° ± 3.3°, -0.4° ± 5° and 6.9° ± 11.4°, respectively. This planning allows accurate implant size prediction. Stem position and cup inclination are accurately reproducible.