The Natural History of Globus Pharyngeus

Globus pharyngeus is a common disorder and accounts for 5% of all ENT referrals. Objectives. To evaluate the role of barium swallow and endoscopy in these patients, to ascertain the incidence, if any, of aerodigestive tract malignancy in this group and to assess the natural evolution of globus pharyngeus. Materials and Methods. Seventy-nine patients underwent barium swallow and rigid oesophagoscopy for globus pharyngeus between January 2005 and October 2008. Fifty-five patients were contacted by phone on average 5 years and 3 months after intervention and asked if their symptoms still persisted. Twenty-four patients were uncontactable or lost to followup, three patients were deceased, two of cardiac related disease and one of renal failure. Results. The majority of patients, 36 of 55 (65%), had a normal barium swallow. Forty-five of 55 (82%) of patients had normal rigid endoscopies. Thirty-one of 55 (56%) patients were at an average followup time of 5 years and 3 months. No patient developed a malignant lesion. Conclusion. Globus pharyngeus is a relatively common but benign condition of indeterminate origin. Our study demonstrates that many of these patients spontaneously improve with time

Open vent volcanoes fuelled by depth-integrated magma degassing

Open-vent, persistently degassing volcanoes—such as Stromboli and Etna (Italy), Villarrica (Chile), Bagana and Manam (Papua New Guinea), Fuego and Pacaya (Guatemala) volcanoes—produce high gas fluxes and infrequent violent strombolian or ‘paroxysmal’ eruptions that erupt very little magma. Here we draw on examples of open-vent volcanic systems to highlight the principal characteristics of their degassing regimes and develop a generic model to explain open-vent degassing in both high and low viscosity magmas and across a range of tectonic settings. Importantly, gas fluxes from open-vent volcanoes are far higher than can be supplied by erupting magma and independent migration of exsolved volatiles is integral to the dynamics of such systems. The composition of volcanic gases emitted from open-vent volcanoes is consistent with its derivation from magma stored over a range of crustal depths that in general requires contributions from both magma decompression (magma ascent and/or convection) and iso- and polybaric second boiling processes. Prolonged crystallisation of water-rich basalts in crustal reservoirs produces a segregated exsolved hydrous volatile phase that may flux through overlying shallow magma reservoirs, modulating heat flux and generating overpressure in the shallow conduit. Small fraction water-rich melts generated in the lower and mid-crust may play an important role in advecting volatiles to subvolcanic reservoirs. Excessive gas fluxes at the surface are linked to extensive intrusive magmatic activity and endogenous crustal growth, aided in many cases by extensional tectonics in the crust, which may control the longevity and activity of open-vent volcanoes. There is emerging abundant geophysical evidence for the existence of a segregated exsolved magmatic volatile phase in magma storage regions in the crust. Here we provide a conceptual picture of gas-dominated volcanoes driven by magmatic intrusion and degassing throughout the crust

Nasal Birth Trauma: A Review of Appropriate Treatment

The aetiology of nasal deformity has frequently included birth trauma. There is no consensus in the literature as to whether nasal surgery, in the form of closed reduction, is indicated in neonates. The majority of studies in the literature that advocate intervention have inadequate followup periods and there is a paucity of evidence for the adverse effects of conservative management. This case highlights the therapeutic dilemma posed by such nasal injuries in the neonate and, to the best of the authors' knowledge, at the time of writing, represents the earliest reported case in the literature of nasal deformity in the neonate. The term nasal deformity is used to denote deformity of the nasal pyramid, soft tissue, and septum. Three main aspects of neonatal nasal deformity are addressed including, firstly, if nasal deformity at birth needs to be addressed, secondly, if left unaltered, what the long-term effects are and, finally, if intervention alters the normal course of midfacial development

Is Creutzfeldt-Jakob disease transmitted in blood?

Creutzfeldt-Jakob disease (CJD) has been considered infectious since the mid-1960s, but its transmissibility through the transfusion of blood or blood products is controversial. The causative agent's novel undefined nature and resistance to standard decontamination, the absence of a screening test, and the recognition that even rare cases of transmission may be unacceptable have led to the revision of policies and procedures worldwide affecting all facets of blood product manufacturing from blood collection to transfusion. We reviewed current evidence that CJD is transmitted through blood

A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49•58°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) versus achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95% lower CI) serum 25(OH)D (nmol/l) = 9•2 (8•5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35µg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0•044 × (total vitamin D) + 33•035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95% lower CI curvilinear and linear models predicted a serum 25(OH)D of 54•4 and 55•2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95% range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake–status relationship needs to be considered carefully when setting new reference intake values in Europe

Petrologic monitoring at Volcán de Fuego, Guatemala

Paroxysmal activity represents an end-member in the common range of activity at mafic arc volcanoes, characterised by rapid transitions across the effusive-explosive interface and thus posing significant challenges to hazard assessment. Conceptual models to explain changes in the frequency and magnitude of these paroxysmal events are based either on magma recharge or an increase in gas flux, largely framed in the context of two-phase flow. Gas- and magma-driven models are both viable mechanisms to explain the varying styles of paroxysmal behaviour observed in mafic systems; however, each has different implications for future activity. We present time series petrologic data for ash and lava samples collected at Volcán de Fuego, Guatemala, during paroxysmal eruptions between 2011 and 2018. We show that a step-change in glass composition occurred between 2015 and 2016, reflecting an increase in magma temperature and a reduction in pre-eruptive crystallisation, concurrent with an escalation in the frequency of paroxysmal activity. There was no change in the bulk or phase compositions during this period. To explain these observations, we propose that the increase in frequency of paroxysmal eruptions is modulated by the supply of exsolved volatiles from lower crustal degassing magmas, without invoking repeated transfer of new, primitive magma to a shallow reservoir. Protracted lava effusion, accompanied by more vigorous and more frequent Strombolian explosions and gas ‘chugging’, prior to the transition to sustained fountaining suggests that gas retention in crystal-rich magma may modulate the height of the magma column as gas supply increases. Slow decompression associated with effusion may determine the timing of effusive to explosive transitions in mafic arc systems more generally. A large paroxysmal eruption of Fuego on 3 June 2018, notable for the rapid escalation in eruptive intensity several hours into the eruption, produced ash with a range of textures and glass compositions consistent with magma evacuation over a range of depths and decompression rates. Given the protracted repose time between paroxysms before this event, we suggest that a shallow crystallised plug degraded, and ultimately failed, several hours into the eruption of 3 June 2018, triggering top-down decompression of magma in the conduit synchronous with the observed rapid acceleration in eruption rate. Ultimately, we propose that the frequency of paroxysms at Fuego is broadly proportional to the gas supply rate, while the range in glass compositions is related to the repose time prior to eruptive activity. Our data illustrate the potential of petrologic monitoring to distinguish between gas- and magma-driven paroxysm triggers and to anticipate future events, especially when interpreted in the context of geophysical observations and implemented within community-based ash collection initiatives

Recombinase-based conditional and reversible gene regulation via XTR alleles

Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap. We validate our approach by targeting the p53 and Rb genes and establishing cell line and in vivo cancer model systems, to study the impact of p53 or Rb inactivation and restoration. We term this allele system XTR, to denote each of the allelic states and the associated expression patterns of the targeted gene: eXpressed (XTR), Trapped (TR) and Restored (R)

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations

When size really does matter - providing PrEP across Queensland

Background: Providing universal access to PrEP across Queensland, the 2nd largest and 3rd most populous state in Australia has provided unique challenges. Queensland has 22.5% of Australia’s total land area, compared to the 14.4% of New South Wales, Victoria and Tasmania combined. Queensland is also less centralised with 50% of the population living outside the state capital and 25% outside of the south eastern region. Notably, this population distribution is reflected in HIV diagnoses with 24% of new diagnoses in 2015 coming from Health Service Areas outside of the south east. Method: The unique service models, buildings, personalities, communities and clinical capacity of regional services has required bespoke solutions to implement QPrEPd in these sites. Many sites have not taken part in clinical trials before and required additional support. Additionally, the barriers to access found in more conservative services and communities has required the implementation team to advocate and educate for universal PrEP provision. Protocol modification has enabled nurses to manage ongoing PrEP provision in services with limited medical officer support. Results: Eleven study sites are outside of the south east corner; 7 public sexual health services, 3 general practices in Cairns and one Aboriginal Medical Service in Toowoomba. These sites have enrolled 18.5% of the all participants. The remaining 11 sites in the south east corner are include 5 general practices, including one run through a community based organisation, 5 public sexual health clinics and one private hospital. Overall, nearly 63% of the participants have enrolled at general practice sites. Conclusions: While this project has provided access to PrEP throughout much of Queensland, gaps remain. The key limitation in regional areas where there is no public sexual health service is the lack of S100 prescribing general practitioners. In order to expand access other service delivery models are being explored