A Holistic View of Identity Theft Tax Refund Fraud

This thesis attempts to explain what identity theft tax refund fraud is and how the issue has developed over the years. It presents a holistic, historic view of the problem as well as how it has been addressed. It primarily relies on reports from the Internal Revenue Service (IRS), Treasury Inspector General for Tax Administration (TIGTA), Government Accountability Office (GAO) and National Taxpayer Advocate (NTA) in its assessment. It does not examine foreign tax administrations’ methods of dealing with identity theft refund fraud or the extent of the issue in other principalities, and therefore this is an area in need of further research. This thesis does not attempt to make an argument for the efficacy of funding for the IRS either, which is an area that could be further studied. It also does not deal with employment-related identity fraud, which some relate to identity theft refund fraud

Multilingual classrooms: opportunities and challenges for English medium instruction in low and middle income contexts

This report is the product of a research collaboration between Education Development Trust, the British Council and The Open University. Its starting point was to consider the complex field of English Medium Instruction (EMI) policies in low and middle income countries (LMICs). Its purpose is to provide insight and support to those responsible for setting policy or enacting it in complex language environments around the world. The work recognises the importance given to English language by governments in the future development of intellectual and economic capital, and to accessing opportunity in an increasingly global world. It also recognises and respects the strong argument calling for education and learning to be conducted in a language spoken by learners and teachers. Navigating these two influences can appear impossible at times as they can be unhelpfully positioned as opposites. This research study set out to do two things: • Look at the global literature and draw on the lessons from existing research. • Focus on illustrating the operational enactment and levels of understanding of EMI polices in schools in two primary school contexts – Ghana and Bihar, India. These very different contexts provide valuable lessons that will help policy makers, educators, teacher trainers and schools to navigate the complexities of multilingual EMI environments

Crystal Structure of the P Pilus Rod Subunit PapA

P pili are important adhesive fibres involved in kidney infection by uropathogenic Escherichia coli strains. P pili are assembled by the conserved chaperone-usher pathway, which involves the PapD chaperone and the PapC usher. During pilus assembly, subunits are incorporated into the growing fiber via the donor-strand exchange (DSE) mechanism, whereby the chaperone's G1 β-strand that complements the incomplete immunoglobulin-fold of each subunit is displaced by the N-terminal extension (Nte) of an incoming subunit. P pili comprise a helical rod, a tip fibrillum, and an adhesin at the distal end. PapA is the rod subunit and is assembled into a superhelical right-handed structure. Here, we have solved the structure of a ternary complex of PapD bound to PapA through donor-strand complementation, itself bound to another PapA subunit through DSE. This structure provides insight into the structural basis of the DSE reaction involving this important pilus subunit. Using gel filtration chromatography and electron microscopy on a number of PapA Nte mutants, we establish that PapA differs in its mode of assembly compared with other Pap subunits, involving a much larger Nte that encompasses not only the DSE region of the Nte but also the region N-terminal to it. Author Summary. Bacterial adhesion to a host is a crucial step that determines the onset of bacterial infection. It is mediated through recognition of a receptor on the host cell surface by a protein called an adhesin displayed on the surface of the bacterium. Many adhesins are displayed at the tip of specialized organelles called pili, some of which are assembled by the ubiquitous chaperone-usher pathway. In this pathway, each pilus subunit is assisted in folding by a chaperone. The resulting chaperone-subunit complex is targeted to a pore located in the outer membrane, called the usher, that serves as assembly platform. There, pilus subunits dissociate from the chaperone and polymerize, resulting in a surface organelle, the pilus, that protrudes out of the usher. Here, we have determined the structure of the major subunit of the P pilus, PapA. The P pilus, produced in uropathogenic Escherichia coli, displays the adhesin PapG responsible for targeting the bacterium to the kidney epithelium. We have determined the structure of PapA either bound to its cognate chaperone, PapD, or bound to another PapA subunit. These structures provide a view of PapA before and after its assembly in the pilus and shed light on the mechanism of PapA assembly.National Institutes of Health (DE 09761, GM040388, DE 09161); Committee of Scientific Research (3 PO4A 003 24, 2 P05A 137 24); Foundation for Polish Science (SUBSYDIUM PROFESORSKIE award); Swedish Rheumatism Association; Nanna Svartz Foundation; King Gustaf V Foundatio

What does it take to stick around?: Molecular insights into biofilm formation by uropathogenic Escherichia coli

Existence in the biofilm state lends bacteria the opportunity to enjoy, at least for a finite amount of time, the benefits of a multicellular entity. The order of events leading to biofilm formation and disassembly has been the topic of interest for numerous studies, aiming to identify factors and mechanisms that underlie this dynamic developmental process. Of particular import is research leveraged at delineating biofilm formation by medically relevant microorganisms, as prevention or eradication of biofilm from medical devices and from within the host pose a serious challenge in the healthcare setting. Recent research describes how a transcriptional regulator modulates biofilm formation in uropathogenic Escherichia coli (UPEC) by affecting the expression of the type 1 adhesive organelles in response to extracellular signals

Different Disease Profiles for Women and Men with Abdominal Aortic Aneurysms

ObjectiveThe overall aim with this study was to investigate causes of death and mortality rates for women and men treated for abdominal aortic aneurysm (AAA) in Sweden.Materials and methodAll patients treated for ruptured and non-ruptured AAA 1987–2002 in Sweden were identified in national registries (n=12917). Age, sex, diagnosis, surgical procedure and mortality were analysed on a patient specific level. Logistic regression and analysis of standardised mortality rates (SMR) were performed.ResultsPost operative mortality was similar between the sexes. Age (p<0.0001), and surgery for rupture (p=0.0005), but not gender (p=0.65) were significant risk factor for poor long term survival. SMR revealed increased risk for both sexes compared to the population with significantly higher values for women than men (2.26, CI 2.10–2.43 vs. 1.63, CI 1.57–1.68, p<0.0001). The higher risk for women could be explained by the higher risk for aneurysm related death (ie.thoracic or abdominal aorta) compared to men (Hazard ratio 1.57 vs. 1.0, p<0.0001).ConclusionWomen do not have an increased surgical risk compared to men, but treated women have an increased risk of premature death compared to men and women in the population. They also have a higher risk for aneurysm related death compared to men with AAA

Host and bacterial proteases influence biofilm formation and virulence in a murine model of enterococcal catheter-associated urinary tract infection

Urinary tract infections: targeting enzymes might help Identifying bacterial and host enzymes that support biofilm formation may help prevent urinary tract infections caused by catheters. Enterococcus faecalis bacteria is a leading cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infections. Michael Caparon and colleagues at Washington University School of Medicine in Missouri, USA, studied these infections in mice. They examined the effects of two protein-degrading enzymes, both from the bacterium and one can be activated by urine trypsin-like protease from the animals. Mutations that impaired either one of the enzymes had no effect on the infection, but when both the bacterial enzymes were impaired by mutation the formation of biofilms was significantly reduced. Treating the mice with chemicals that inhibited both bacterial and host enzymes dramatically reduced catheter-induced inflammation and related problems. This suggests drugs targeting these enzymes could be useful in clinical care

Urinary tract infections trigger synucleinopathy via the innate immune response

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also be important triggers of MSA. We performed an epidemiological nested-case control study in the Danish population showing that UTIs are associated with future diagnosis of MSA several years after infection and that it impacts risk in both men and women. Bacterial infection of the urinary bladder triggers synucleinopathy in mice and we propose a novel role of ɑSyn in the innate immune system response to bacteria. Urinary tract infection with uropathogenic E. coli results in the de novo aggregation of ɑSyn during neutrophil infiltration. During the infection, ɑSyn is released extracellularly from neutrophils as part of their extracellular traps. Injection of MSA aggregates into the urinary bladder leads to motor deficits and propagation of ɑSyn pathology to the central nervous system in mice overexpressing oligodendroglial ɑSyn. Repeated UTIs lead to progressive development of synucleinopathy with oligodendroglial involvement in vivo. Our results link bacterial infections with synucleinopathy and show that a host response to environmental triggers can result in ɑSyn pathology that bears semblance to MSA

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens

Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection

Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The mechanism behind this increased risk is unknown; however, bacteriuria increases immediately after sexual intercourse episodes, suggesting that physical manipulation introduces periurethral flora into the urinary tract. In this paper, we investigated whether superinfection (repeat introduction of bacteria) resulted in increased risk of severe UTI, manifesting as persistent bacteriuria, high titer bladder bacterial burdens and chronic inflammation, an outcome referred to as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial replication and is defined histologically by urothelial hyperplasia and submucosal lymphoid aggregates, a histological pattern similar to that seen in humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis after a single infection; however, they developed persistent bacteriuria and chronic cystitis when superinfected 24 hours apart. Elevated levels of interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony-stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second infection predicted the development of chronic cystitis. These same cytokines have been found to precede chronic cystitis in singly infected C3H/HeN mice. Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the proportion of mice that developed chronic cystitis. Intracellular bacterial replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation were essential for this increase. Microarrays conducted at four weeks post inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial peptides during chronic cystitis. These data suggest a mechanism by which caspase-1/11 activation and IL-1 secretion could predispose certain women to recurrent UTI after frequent intercourse, a predisposition predictable by several serum biomarkers in two murine models