A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.

Introduction to "Business innovation and disruption in the music industry"

Similar to most other creative industries, the evolution of the music industry is heavily shaped by media technologies. This was equally true in 1999, when the global recorded music industry had experienced two decades of continuous growth largely driven by the rapid transition from vinyl records to Compact Discs. The transition encouraged avid music listeners to purchase much of their music collections all over again in order to listen to their favourite music with ‘digital sound’. As a consequence of this successful product innovation, recorded music sales (unit measure) more than doubled between the early 1980s and the end of the 1990s. It was with this backdrop that the first peer-to-peer file sharing service was developed and released to the mainstream music market in 1999 by the college student Shawn Fanning. The service was named Napster and it marks the beginning of an era that is now a classic example of how an innovation is able to disrupt an entire industry and make large swathes of existing industry competences obsolete. File sharing services such as Napster, followed by a range of similar services in its path, reduced physical unit sales in the music industry to levels that had not been seen since the 1970s. The severe impact of the internet on physical sales shocked many music industry executives who spent much of the 2000s vigorously trying to reverse the decline and make the disruptive technologies go away. At the end, they learned that their efforts were to no avail and the impact on the music industry proved to be transformative, irreversible and, to many music industry professionals, also devastating. Thousands of people lost their livelihood, large and small music companies have folded or been forced into mergers or acquisitions. But as always during periods of disruption, the past 15 years have also been very innovative, spurring a plethora of new music business models. These new business models have mainly emerged outside the music industry and the innovators have been often been required to be both persuasive and persistent in order to get acceptance from the risk-averse and cash-poor music industry establishment. Apple was one such change agent that in 2003 was the first company to open up a functioning and legal market for online music. iTunes Music Store was the first online retail outlet that was able to offer the music catalogues from all the major music companies; it used an entirely novel pricing model, and it allowed consumers to de-bundle the music album and only buy the songs that they actually liked. Songs had previously been bundled by physical necessity as discs or cassettes, but with iTunes Music Store, the institutionalized album bundle slowly started to fall apart. The consequences had an immediate impact on music retailing and within just a few years, many brick and mortar record stores were forced out of business in markets across the world. The transformation also had disruptive consequences beyond music retailing and redefined music companies’ organizational structures, work processes and routines, as well as professional roles. iTunes Music Store in one sense was a disruptive innovation, but it was at the same time relatively incremental, since the major labels’ positions and power structures remained largely unscathed. The rights holders still controlled their intellectual properties and the structures that guided the royalties paid per song that was sold were predictable, transparent and in line with established music industry practices.

Energy expenditure and the body cell mass in cystic fibrosis

Poor nutritional status in patients with cystic fibrosis (CF) is associated with severe lung disease, and possible causative factors include inadequate intake, malabsorption, and increased energy requirements. Body cell mass (which can be quantified by measurement of total body potassium) provides an ideal standard for measurements of energy expenditure. The aim of this study was to compare resting energy expenditure (REE) in patients with CF with both predicted values and age-matched healthy children and to determine whether REE was related to either nutritional status or pulmonary function. REE was measured by indirect calorimetry and body cell mass by scanning with total body potassium in 30 patients with CF (12 male, mean age = 13.07 ± 0.55 y) and 18 healthy children (six male, mean age = 12.56 ± 1.25 y). Nutritional status was expressed as a percentage of predicted total body potassium. Lung function was measured in the CF group by spirometry and expressed as the percentage of predicted forced expiratory volume in 1 s. Mean REE was significantly increased in the patients with CF compared with healthy children (119.3 ± 3.1% predicted versus 103.6 ± 5% predicted, P < 0.001) and, using multiple regression techniques, REE for total body potassium was significantly increased in patients with CF (P = 0.0001). There was no relation between REE and nutritional status or pulmonary disease status in the CF group. In conclusion, REE is increased in children and adolescents with CF but is not directly related to nutritional status or pulmonary disease.

Design of multi-frequency microstrip antennas using multiple rings

An electromagnetically coupled feed arrangement is proposed for simultaneously exciting multiple concentric ring antennas for multi-frequency operation. This has a multi-layer dielectric configuration in which a transmission line is embedded below the layer containing radiating rings. Energy coupled to these rings from the line beneath is optimised by suitably adjusting the location and dimensions of stubs on the line. It has been shown that the resonant frequencies of these rings do not change as several of these single-frequency antennas are combined to form a multi-resonant antenna. Furthermore, all radiators are forced to operate at their primary mode and some harmonics of the lower resonant frequency rings appearing within the frequency range are suppressed when combined. The experimental prototype antenna has three resonant frequencies at which it has good radiation characteristics.

An automated emergency landing system for fixed-wing aircraft: Planning and control

A number of hurdles must be overcome in order to integrate unmanned aircraft into civilian airspace for routine operations. The ability of the aircraft to land safely in an emergency is essential to reduce the risk to people, infrastructure and aircraft. To date, few field-demonstrated systems have been presented that show online re-planning and repeatability from failure to touchdown. This paper presents the development of the Guidance, Navigation and Control (GNC) component of an Automated Emergency Landing System (AELS) intended to address this gap, suited to a variety of fixed-wing aircraft. Field-tested on both a fixed-wing UAV and Cessna 172R during repeated emergency landing experiments, a trochoid-based path planner computes feasible trajectories and a simplified control system executes the required manoeuvres to guide the aircraft towards touchdown on a predefined landing site. This is achieved in zero-thrust conditions with engine forced to idle to simulate failure. During an autonomous landing, the controller uses airspeed, inertial and GPS data to track motion and maintains essential flight parameters to guarantee flyability, while the planner monitors glide ratio and re-plans to ensure approach at correct altitude. Simulations show reliability of the system in a variety of wind conditions and its repeated ability to land within the boundary of a predefined landing site. Results from field-tests for the two aircraft demonstrate the effectiveness of the proposed GNC system in live operation. Results show that the system is capable of guiding the aircraft to close proximity of a predefined keyhole in nearly 100% of cases.

The physics of ENSO-monsoon connection

The physical mechanism through which Ei-Nino and Southern Oscillation (ENSO) tends to produce deficient precipitation over Indian continent is investigated using both observations as well as a general circulation model. Both analysis of observations and atmospheric general circulation model (AGCM) study show that the planetary scale response associated with ENSO primarily influences the equatorial Indian Ocean region. Through this interaction it tends to favour the equatorial heat source, enhance precipitation over the equatorial Indian Ocean and indirectly cause a decrease in continental precipitation through induced subsidence. This situation is further complicated by the fact the regional tropospheric quasi biennial oscillation (QBO) has a bimodal structure over this region with large amplitude over the Indian continent. While the ENSO response has a quasi-four year periodicity and tends peak during beginning of the calendar year, the QBO mode tends to peak during northern summer. Thus, the QBO mode exerts a stronger influence on the interannual variability of the monsoon. The strength of the Indian monsoon in a given year depends on the combined effect of the ENSO and the QBO mode. Sines the two oscillations have disparate time scales, exact phase information of the two modes during northern summer is important in determining the Indian summer monsoon. The physical mechanism of the interannual variations of the Indian monsoon precipitation associated with ENSO presented here is similar to the physical process that cause intraseasonal 'active', 'break' oscillations of the monsoon.

Infinite Dimensional Slow Modulations In A Delayed Model For Orthogonal Cutting Vibrations

We apply the method of multiple scales (MMS) to a well known model of regenerative cutting vibrations in the large delay regime. By ``large'' we mean the delay is much larger than the time scale of typical cutting tool oscillations. The MMS upto second order for such systems has been developed recently, and is applied here to study tool dynamics in the large delay regime. The second order analysis is found to be much more accurate than first order analysis. Numerical integration of the MMS slow flow is much faster than for the original equation, yet shows excellent accuracy. The main advantage of the present analysis is that infinite dimensional dynamics is retained in the slow flow, while the more usual center manifold reduction gives a planar phase space. Lower-dimensional dynamical features, such as Hopf bifurcations and families of periodic solutions, are also captured by the MMS. Finally, the strong sensitivity of the dynamics to small changes in parameter values is seen clearly.

Sexual harassment: A threat to gradual women emancipation

This article is an attempt to highlight gender-based attitude of society towards women. Women comprise approximately 50% of the total population of Pakistan; Pakistan cannot afford to keep half of its citizens inactive and their potential as participants in development and progress untapped. Nothing more than the misogynist view of women as weak in physical power and deficient in mental faculties has marred the upward movement of societies. Women who defy this erroneous obscurantist conceptualisation and step into public domain are forced either to step back or to make compromises with the situation at the cost of their self-esteem and dignity. This deviant social behaviour is identified as sexual harassment of women. Sexual harassment of women exists beyond geographic spaces, across historic times, and today is prevalent in all societies, developed or underdeveloped. Women are sexually harassed within the safe havens of their homes too. This paper examines how a combination of factors, including religious interpretations, social norms, state negligence, and bad governance result in creating and than perpetuating an anti-women environment that breeds sexual harassment and solidifies patriarchal structures. The last section of this paper cites reported cases of sexual harassment at workplace that happened between 2001 and 2011. Summing up, the paper offers some suggestions to minimise work-place sexual harassment of women.

Shariah perspective on marriage contract and practice in contemporary Muslim societies

Forced marriages are worldwide phenomena and also exist in Pakistani society. It involves the lack of free and full consent of at least one of the parties to a marriage. Mostly, females are victims of forced marriages. It is prevalent in the name of religion in many Muslim countries; however, it is purely a traditional and cultural phenomenon which has nothing to do with religion. Forced marriages are different from arranged marriages in which both parties freely consent to enter into marriage contract and they have no objection on the choice of partner selected by their parents. This study will highlights different forms of forced marriages in Pakistani society.

Nutritional rehabilitation in cystic fibrosis: A 5 year follow-up study

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV, and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p < 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short-and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study. © 1992 Raven Press, Ltd., New York.

Turbulent mixed convection in a shallow enclosure with a series of heat generating components

Turbulent mixed convection flow and heat transfer in a shallow enclosure with and without partitions and with a series of block-like heat generating components is studied numerically for a range of Reynolds and Grashof numbers with a time-dependent formulation. The flow and temperature distributions are taken to be two-dimensional. Regions with the same velocity and temperature distributions can be identified assuming repeated placement of the blocks and fluid entry and exit openings at regular distances, neglecting the end wall effects. One half of such module is chosen as the computational domain taking into account the symmetry about the vertical centreline. The mixed convection inlet velocity is treated as the sum of forced and natural convection components, with the individual components delineated based on pressure drop across the enclosure. The Reynolds number is based on forced convection velocity. Turbulence computations are performed using the standard k– model and the Launder–Sharma low-Reynolds number k– model. The results show that higher Reynolds numbers tend to create a recirculation region of increasing strength in the core region and that the effect of buoyancy becomes insignificant beyond a Reynolds number of typically 5×105. The Euler number in turbulent flows is higher by about 30 per cent than that in the laminar regime. The dimensionless inlet velocity in pure natural convection varies as Gr1/3. Results are also presented for a number of quantities of interest such as the flow and temperature distributions, Nusselt number, pressure drop and the maximum dimensionless temperature in the block, along with correlations.

Left-Handed DNA in Synthetic and Topologically Constrained Form V-DNA

We have investigated structural transitions in Poly(dG-dC) and Poly(dG-Me5dC) in order to understand the exact role of cations in stabilizing left-handed helical structures in specific sequences andthe biological role, if any, of these structures. From a novel temperature dependent transition it has been shown that a minor fluctuation in Na+ concentration at ambient temperature can bring about Β to Ζ transition. Forthe first time, wehave observed a novel double transition in poly(dG-Me5dC) as the Na+ concentration is gradually increased. This suggests that a minor fluctuation in Na+ concentration in conjunction with methylation may transform small stretches of CG sequences from one conformational state to another. These stretches could probably serve as sites for regulation. Supercoiled formV DNA reconstituted from pBR322 and pßG plasmids have been studied as model systems, in order to understand the nature and role of left-handed helical conformation in natural sequences. A large portion of DNA in form V, obtained by reannealing the two complementary singlestranded circles is forced to adopt left-handed double helical structure due to topological constraints (Lk = 0). Binding studies with Z-DNA specific antibody and spectroscopic studies confirm the presence of left-handed Z-structure in the pßG and pßR322 form V DNA. Cobalt hexamine chloride, which induces Z-form in Poly(dG-dC) stabilizes the Z-conformation in form V DNA even in the non-alternating purine-pyrimidine sequences. A reverse effect is observed with ethidium bromide. Interestingly, both topoisomerase I and II (from wheat germ) act effectively on form V DNA to give rise to a species having an electrophoretic mobility on agarose gel similar to that of open circular (form II) DNA. Whether this molecule is formed as a result of the left-handed helical segments of form V DNA undergoing a transition to the right-handed B-form during the topoisomerase action remains to be solved.

Methodological innovation in precarious spaces: The case of Twitter

Social media analytics is a rapidly developing field of research at present: new, powerful ‘big data’ research methods draw on the Application Programming Interfaces (APIs) of social media platforms. Twitter has proven to be a particularly productive space for such methods development, initially due to the explicit support and encouragement of Twitter, Inc. However, because of the growing commercialisation of Twitter data, and the increasing API restrictions imposed by Twitter, Inc., researchers are now facing a considerably less welcoming environment, and are forced to find additional funding for paid data access, or to bend or break the rules of the Twitter API. This article considers the increasingly precarious nature of ‘big data’ Twitter research, and flags the potential consequences of this shift for academic scholarship.

Evaluation of Two MCDM Methods for UAV Emergency Landing

One of the major impediments for the use of UAVs in civilian environment is the capability to replicate some of the functionality of safe manned aircraft operations. One critical aspect is emergency landing. Once the possible landing sites have been rated, a decision on the most suitable choice to land is required. This is a multi-criteria decision making (MCDM) problem which needs to take into account various factors in its selection of landing site. This report summarises relevant literature in MCDM in the context of emergency forced landing and proposes and compares two algorithms and methods for this task.

Simple new PWM patterns for thyristor three-phase AC/DC convertors

Thyristor forced commutated AC/DC convertors are useful for improving the power factor and waveform of AC-side line current. These are controlled through pulse-width modulation schemes for best performance. However, the 3-phase versions impose restrictions on the PWM strategies that can be implemented for excellent harmonic rejection. This paper presents new PWM control strategies for the 3-phase converters and compares them along with the conventional 4-pulse PWM strategy for harmonic elimination. Finally, two new PWM strategies are shown to be the best, for which oscillograms are presented from actual implementation.