A molecular epidemiological analysis of meningococcal isolates within Scotland 1972-1998

Neisseria meningitidis is an important cause of meningitis and bacteraemia worldwide and is associated with high case-fatality rates. Meningococcal disease continues to remain a public health issue in Scotland and the rest of Europe. Typing methods are used for epidemiological purposes to investigate outbreaks and the spread of meningococci and to examine the population structure of the organism in order to better understand its variation and evolution. Reference institutes have employed such methods for a number of decades for the diagnosis and detection of meningococci. However, phenotypic methods for serogrouping, serotyping and serosubtyping meningococci, although providing good strain information, can lead to endemic strains appearing identical using these methods when they are in fact quite different. More recently methods have been developed to further characterise bacteria. These methods have included PCR for the detection of meningococcal disease within blood, serogrouping and sequencing of housekeeping genes (MLST) and antigen genes such as PorA. These molecular epidemiological methods were used for the retrospective typing of invasive meningococci in Scotland, 1972-1998, using a fully automated procedure. The results of these were then analysed using statistical packages to examine the population structure of the organism. In total there were 2517 invasive isolates, received by the Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL) from the start of 1972 to the end of 1998. Serogroup distribution changed from year to year during the time period 1972-1998 but serogroups B and C were dominant throughout this period. Serogroup B was the dominant serogroup throughout the seventies and early eighties until serogroup C became dominant during the mid 1980s. This increase in dominance of serogroup C has been found in this study not to be associated with one particular sequence type (ST) but is associated with a number of STs, which include ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease in the 1990s that was due to the ST-11 clonal complex. While there was much diversity in the STs (309 different STs among the 2517 isolates), only ten accounted for 1562 isolates (59.9%). These were ST-11, ST-8, ST-41, ST-153, ST-1, ST-32, ST-33, ST-269, ST-334 and ST-60. There were 177 new STs found during the time period. The STs were further differentiated into 31 clonal complexes, with 57 singleton types. As with the STs, although there was much diversity in the clonal complexes, only seven accounted for 1993 isolates. It was found that with PorA variable region (VR) types there were certain combinations significantly more common than others. There was a strong link with PorA type and ST and more so with clonal complex. This link was evident with the PorA type 5, 2-1, 36-2, which occured in 70 isolates representing the ST-11 complex and in all but two isolates representing ST-11. Similarly PorA type 18-3, 1, 35-1 was associated with 15 isolates belonging to the ST41-44 complex. However, this was not the case with all PorA combinations as the PorA type 19, 15, 36 was associated with 10 different complexes. There was some association between serogroup and PorA VR types. There was strong evidence of certain VR1, 2 and 3 regions being associated with certain serogroups, although this was not definitive. For example, of 192 isolates with PorA type 19, 15, 36, 85.4% were associated with serogroup B. Genosubtyping of the porA gene has been shown to increase the power of differentiation within clonal meningococcal populations. For, example, seven isolates that had the same serogroup, ST, VR1 and VR2 could be differentiated by their VR3 type. Using cluster detection software SaTScan to analyse all isolates, it was found there were 29 clusters in Scotland, from 1972-1998. These clusters included 63 cases, which accounted for 2.5% of all cases. A range of different strains caused the clusters that were identified in this study, some caused by hypervirulent strains. These strain types were responsible for a number of cases throughout the world as well as in Scotland during the period of this study. However it was also shown that there were clusters identified in this study caused by lesser-known strain types that were not responsible for many cases and that appear to be unique to Scotland or the UK. This study is the first to look at the detection of clusters over a time period of 26 years and to identify clusters that would have previously been unidentified due to lack of suitable characterisation techniques. The results in this study indicate that the multivalent preparation produced by the Netherlands Vaccine Institute (Nonavalent vaccine) had the potential, based on the PorA types that it contains, to prevent the majority of serogroup B infection that had occurred in Scotland, from 1972-1998. It also had the potential, although not to the same extent as serogroup B, to protect against other serogroups. For the age groups that would potentially have been the first to be immunised with any vaccine as part of the childhood vaccination programme, the 0-4 years old group, the potential coverage was over 92% which is comparable with the coverage seen with the serogroup C meningococcal conjugate (MCC) vaccine, of approximately 90%

Flow transitions in two-dimensional foams

For sufficiently slow rates of strain, flowing foam can exhibit inhomogeneous flows. The nature of these flows is an area of active study in both two-dimensional model foams and three dimensional foam. Recent work in three-dimensional foam has identified three distinct regimes of flow [S. Rodts, J. C. Baudez, and P. Coussot, Europhys. Lett. {\bf 69}, 636 (2005)]. Two of these regimes are identified with continuum behavior (full flow and shear-banding), and the third regime is identified as a discrete regime exhibiting extreme localization. In this paper, the discrete regime is studied in more detail using a model two dimensional foam: a bubble raft. We characterize the behavior of the bubble raft subjected to a constant rate of strain as a function of time, system size, and applied rate of strain. We observe localized flow that is consistent with the coexistence of a power-law fluid with rigid body rotation. As a function of applied rate of strain, there is a transition from a continuum description of the flow to discrete flow when the thickness of the flow region is approximately 10 bubbles. This occurs at an applied rotation rate of approximately $0.07 {\rm s^{-1}}$

Clonal analysis of meningococci during a 26 year period prior to the introduction of meningococcal serogroup C vaccines

Meningococcal disease remains a public health burden in the UK and elsewhere. Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were characterised retrospectively to examine the serogroup and clonal structure of the circulating population. 2607 isolates causing invasive disease were available for serogroup and MLST analysis whilst 2517 were available for multilocus sequence typing (MLST) analysis only. Serogroup distribution changed from year to year but serogroups B and C were dominant throughout. Serogroup B was dominant throughout the 1970s and early 1980s until serogroup C became dominant during the mid-1980s. The increase in serogroup C was not associated with one particular sequence type (ST) but was associated with a number of STs, including ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease seen in the 1990s that was due to expansion of the ST-11 clonal complex. While there was considerable diversity among the isolates (309 different STs among the 2607 isolates), a large proportion of isolates (59.9%) were associated with only 10 STs. These data highlight meningococcal diversity over time and the need for ongoing surveillance during the introduction of new meningococcal vaccines

Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells

Proper regulation of cytosolic Ca2+ is critical for pancreatic acinar cell function. Disruptions in normal Ca2+ concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca2+ homeostasis by promoting rapid Ca2+ movement. Determining how expression of Ca2+ modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca2+ ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2’s 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca2+. RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca2+ levels. Combined, these results suggest SPCA2C affects Ca2+ homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca2+ ATPases. J. Cell. Physiol. 231: 2768–2778, 2016. © 2016 Wiley Periodicals, Inc

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Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders.ConclusionsThe results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior

Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV

Pion-nucleus elastic scattering at energies above the Delta(1232) resonance is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies, and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment

kb_DRAM: annotation and metabolic profiling of genomes with DRAM in KBase

Microbial genome annotation is the process of identifying structural and functional elements in DNA sequences and subsequently attaching biological information to those elements. DRAM is a tool developed to annotate bacterial, archaeal, and viral genomes derived from pure cultures or metagenomes. DRAM goes beyond traditional annotation tools by distilling multiple gene annotations to genome level summaries of functional potential. Despite these benefits, a downside of DRAM is the requirement of large computational resources, which limits its accessibility. Further, it did not integrate with downstream metabolic modeling tools that require genome annotation. To alleviate these constraints, DRAM and the viral counterpart, DRAM-v, are now available and integrated with the freely accessible KBase cyberinfrastructure. With kb_DRAM users can generate DRAM annotations and functional summaries from microbial or viral genomes in a point-and-click interface, as well as generate genome-scale metabolic models from DRAM annotations.Availability and implementationFor kb_DRAM users, the kb_DRAM apps on KBase can be found in the catalog at https://narrative.kbase.us/#catalog/modules/kb_DRAM. For kb_DRAM users, a tutorial workflow with all documentation is available at https://narrative.kbase.us/narrative/129480. For kb_DRAM developers, software is available at https://github.com/shafferm/kb_DRAM