Global Patterns of City Size Distributions and Their Fundamental Drivers

Urban areas and their voracious appetites are increasingly dominating the flows of energy and materials around the globe. Understanding the size distribution and dynamics of urban areas is vital if we are to manage their growth and mitigate their negative impacts on global ecosystems. For over 50 years, city size distributions have been assumed to universally follow a power function, and many theories have been put forth to explain what has become known as Zipf's law (the instance where the exponent of the power function equals unity). Most previous studies, however, only include the largest cities that comprise the tail of the distribution. Here we show that national, regional and continental city size distributions, whether based on census data or inferred from cluster areas of remotely-sensed nighttime lights, are in fact lognormally distributed through the majority of cities and only approach power functions for the largest cities in the distribution tails. To explore generating processes, we use a simple model incorporating only two basic human dynamics, migration and reproduction, that nonetheless generates distributions very similar to those found empirically. Our results suggest that macroscopic patterns of human settlements may be far more constrained by fundamental ecological principles than more fine-scale socioeconomic factors

Consumer perceptions of co-branding alliances: Organizational dissimilarity signals and brand fit

This study explores how consumers evaluate co-branding alliances between dissimilar partner firms. Customers are well aware that different firms are behind a co-branded product and observe the partner firms’ characteristics. Drawing on signaling theory, we assert that consumers use organizational characteristics as signals in their assessment of brand fit and for their purchasing decisions. Some organizational signals are beyond the control of the co-branding partners or at least they cannot alter them on short notice. We use a quasi-experimental design and test how co-branding partner dissimilarity affects brand fit perception. The results show that co-branding partner dissimilarity in terms of firm size, industry scope, and country-of-origin image negatively affects brand fit perception. Firm age dissimilarity does not exert significant influence. Because brand fit generally fosters a benevolent consumer attitude towards a co-branding alliance, the findings suggest that high partner dissimilarity may reduce overall co-branding alliance performance

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus

The purpose of this study was to report the effect of combining the Kestenbaum procedure with posterior fixation suture for infantile horizontal nystagmus with anomalous head posture (AHP) in children. Nine consecutive patients who underwent combined Kestenbaum procedure plus posterior fixation suture to the recessed muscles at the same time were retrospectively studied. All patients were orthotropic before surgery and were followed for at least 6 months. Pre- and postoperative AHP and binocular corrected visual acuity (BCVA), and ocular alignment were assessed. Mean age at surgery was 4.8 ± 1.5 years. The average follow-up was 29.7 months. The average head turn preoperatively was 27.4° and postoperatively 7.2°. The average net change in AHP was 24.8° (P = 0.008). Seven of 9 patients (78%) achieved a residual head turn of 10° or less. The average Log Mar BCVA was 0.33 preoperatively and 0.31 postoperatively (P = 0.68). Only 1 patient needed additional surgery for residual horizontal AHP. No patient developed strabismus. Combined Kestenbaum procedure with posterior fixation suture was an effective and stable procedure in reducing AHP of the range of 20° to 35° in children with infantile nystagmus

Condom Negotiations among Female Sex Workers in the Philippines: Environmental Influences

BackgroundSocial and structural influences of condom negotiation among female sex workers (FSWs) remain understudied. This study assesses environmental and individual factors associated with condom negotiation among FSWs at high risk for acquiring HIV in a large urban setting of Metro Manila, Philippines.MethodsFemale bar/spa workers (N = 498), aged 18 and over, underwent interview-led surveys examining their sexual health practices in the context of their risk environments. Data were collected from April 2009-January 2010 from 54 venues. Multiple logistic regressions were conducted to assess socio-behavioral factors (e.g., age, education, length of time employed as an entertainer, and alcohol/drug use) and socio-structural factors (e.g., venue-level peer/manager support, condom rule/availability, and sex trafficking) associated with condom negotiation, adjusting for individuals nested within venues.ResultsOf 142 FSWs who traded sex in the previous 6 months (included in the analysis), 24% did not typically negotiate condom use with venue patrons. Factors in the physical environment--trafficked/coerced into work (AOR = 12.92, 95% CI = 3.34-49.90), economic environment--sex without a condom to make more money (AOR = 1.52, 95% CI 1.01-2.30), policy environment--sex without a condom because none was available (AOR = 2.58, 95% CI = 1.49-4.48), and individual risk--substance use (AOR = 2.36, 95% CI = 1.28-4.35) were independently associated with FSWs' lack of condom negotiation with venue patrons.ConclusionsFactors in the physical, economic, and policy environments, over individual (excepting substance use) and social level factors, were significantly associated with these FSWs' condom negotiations in the Philippines. Drawing upon Rhodes' risk environment framework, these results highlight the need for policies that support safer sex negotiations among sex workers in the context of their risk environments. Interventions should reduce barriers to condom negotiation for FSWs trafficked/coerced into their work, substance using, and impacted by economic conditions and policies that do not support condom availability

A novel approach in the treatment of neuroendocrine gastrointestinal tumors: Additive antiproliferative effects of interferon-γ and meta-iodobenzylguanidine

BACKGROUND: Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG) and interferon-γ (IFNγ) cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNγ and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells. METHODS AND RESULTS: IFNγ receptors were expressed in both models. IFNγ dose- and time-dependently inhibited the growth of both STC-1 and of BON tumor cells with IC(50)-values of 95 ± 15 U/ml and 135 ± 10 U/ml, respectively. Above 10 U/ml IFNγ induced apoptosis-specific caspase-3 activity in a time-dependent manner in either cell line and caused a dose-dependent arrest in the S-phase of the cell cycle. Furthermore, IFNγ induced cytotoxic effects in NE tumor cells. The NE tumor-targeted drug MIBG is selectively taken up via norepinephrine transporters, thereby specifically inhibiting growth in NE tumor cells. Intriguingly, IFNγ treatment induced an upregulation of norepinephrine transporter expression in neuroendocrine tumors cells, as determined by semi-quantitative RT-PCR. Co-application of sub-IC(50 )concentrations of IFNγ and MIBG led to additive growth inhibitory effects, which were mainly due to increased cytotoxicity and S-phase arrest of the cell cycle. CONCLUSION: Our data show that IFNγ exerts antiproliferative effects on neuroendocrine gastrointestinal tumor cells by inducing cell cycle arrest, apoptosis and cytotoxicity. The combination of IFNγ with the NE tumor-targeted agent MIBG leads to effective growth control at reduced doses of either drug. Thus, the administration of IFNγ alone and more so, in combination with MIBG, is a promising novel approach in the treatment of neuroendocrine gastrointestinal tumors

Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus

Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1M146L/APP751SL mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin–cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal Aβ oligomers were identified, the presence of A11-immunopositive Aβ plaques also suggested a direct role of plaque-associated Aβ oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages

Predictors of low cervical cancer screening among immigrant women in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Disparities in cervical cancer screening are known to exist in Ontario, Canada for foreign-born women. The relative importance of various barriers to screening may vary across ethnic groups. This study aimed to determine how predictors of low cervical cancer screening, reflective of sociodemographics, the health care system, and migration, varied by region of origin for Ontario's immigrant women.</p> <p>Methods</p> <p>Using a validated billing code algorithm, we determined the proportion of women who were not screened during the three-year period of 2006-2008 among 455 864 identified immigrant women living in Ontario's urban centres. We created eight identical multivariate Poisson models, stratified by eight regions of origin for immigrant women. In these models, we adjusted for various sociodemographic, health care-related and migration-related variables. We then used the resulting adjusted relative risks to calculate population-attributable fractions for each variable by region of origin.</p> <p>Results</p> <p>Region of origin was not a significant source of effect modification for lack of recent cervical cancer screening. Certain variables were significantly associated with lack of screening across all or nearly all world regions. These consisted of not being in the 35-49 year age group, residence in the lowest-income neighbourhoods, not being in a primary care patient enrolment model, a provider from the same region, and not having a female provider. For all women, the highest population-attributable risk was seen for not having a female provider, with values ranging from 16.8% [95% CI 14.6-19.1%] among women from the Middle East and North Africa to 27.4% [95% CI 26.2-28.6%] for women from East Asia and the Pacific.</p> <p>Conclusions</p> <p>To increase screening rates across immigrant groups, efforts should be made to ensure that women have access to a regular source of primary care, and ideally access to a female health professional. Efforts should also be made to increase the enrolment of immigrant women in new primary care patient enrolment models.</p