Quality of life of patients treated surgically for head and neck cancer

The quality of survival of 48 patients treated surgically for head and neck cancer was assessed using a problem-orientated self-administered questionnaire. The questionnaire was based on the European Organization for Research into the Treatment of Cancer (EORTC) core questionnaire to which a specific head and neck module was added. The following domains were studied: pain, fatigue, physical symptoms (gastrointestinal and 'other'), functional activity, psychological symptoms, overall physical condition and overall quality of life. For the analysis, five groups of patients were considered: laryngectomy (n = 15), pharyngolaryngoesophagectomy (n = 5), craniofacial procedure (n = 11), 'other operations' (n = 9) and patients with disease recurrence (n = 8). Each group identified different problem areas. Laryngectomees and 'other operation' patients reported relatively few problems, whereas patients with disease recurrence described difficulties in all of the domains examined. Symptoms of fatigue were common. Information collected in this way may facilitate improved rehabilitation and thus better quality of survival

The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules

The pharmacokinetics of taurolidine metabolites in healthy volunteers.

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the end of infusion for taurinamide, whereas that of taurultam was reached before completion of infusion. The taurolidine metabolite taurultam demonstrated a shorter half-life and lower systemic exposure than taurinamide. Shortening of infusion duration increased the C(max) and AUC of taurultam. Changes in infusion rate did not substantially change the pharmacokinetic parameters of taurinamide

MK-0448, a Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics and Pharmacodynamic Electrophysiology in Experimental Animal Models and in Humans.

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led to a two-part first-in-human study: Part I evaluated safety and pharmacokinetics, and Part II was an invasive electrophysiologic (EP) study in healthy subjects. MK-0448 was well-tolerated with mild adverse experiences, most commonly irritation at the injection site. During the EP study, ascending doses of MK-0448 were administered, but no increases in atrial or ventricular refractoriness were detected despite achieving plasma concentrations in excess of 2 μM. Follow-up studies in normal anesthetized dogs designed to assess the influence of autonomic tone demonstrated that prolongation of atrial refractoriness with MK-0448 was markedly attenuated in the presence of vagal nerve simulation, suggesting that the effects of I(Kur) blockade on atrial repolarization may be negated by enhanced parasympathetic neural tone. CONCLUSIONS: -The contribution of I(Kur) to human atrial electrophysiology is less prominent than in preclinical models and therefore is likely to be of limited therapeutic value for the prevention of atrial fibrillation

Access to specialist cancer care: is it equitable?

The first principle of the Calman–Hine report's recommendations on cancer services was that all patients should have access to a uniformly high quality of care wherever they may live. This study aimed to assess whether the uptake of chemotherapy for colorectal cancer varied by hospital type in Scotland. Hospitals were classified according to cancer specialisation rather than volume of patients. To indicate cancer specialisation, hospitals were classified as ‘cancer centres’, ‘cancer units’ and ‘non-cancer’ hospitals. Colorectal cancer cases were obtained from cancer registrations linked to hospital discharge data for the period January 1992 to December 1996. Multilevel logistic regression was used to model the binary outcome, namely whether or not a patient received chemotherapy within 6 months of first admission to any hospital. The results showed that patients admitted first to a ‘non-cancer’ hospital were less than half as likely to go on to receive chemotherapy as those first admitted to a cancer unit or centre (OR=0.28). This result was not explained by distance between hospital of first admission and nearest cancer centre, nor by increasing age or severity of illness. The study covers the period immediately preceding the introduction of the Calman–Hine report in Scotland and should serve as a baseline for future monitoring of access to specialist care

The Current State of Performance Appraisal Research and Practice: Concerns, Directions, and Implications

On the surface, it is not readily apparent how some performance appraisal research issues inform performance appraisal practice. Because performance appraisal is an applied topic, it is useful to periodically consider the current state of performance research and its relation to performance appraisal practice. This review examines the performance appraisal literature published in both academic and practitioner outlets between 1985 and 1990, briefly discusses the current state of performance appraisal practice, highlights the juxtaposition of research and practice, and suggests directions for further research

Warm ice giant GJ 3470b - II. Revised planetary and stellar parameters from optical to near-infrared transit photometry

It is important to explore the diversity of characteristics of low-mass, low-density planets to understand the nature and evolution of this class of planets. We present a homogeneous analysis of 12 new and 9 previously published broad-band photometric observations of the Uranus-sized extrasolar planet GJ 3470b, which belongs to the growing sample of sub-Jovian bodies orbiting M dwarfs. The consistency of our analysis explains some of the discrepancies between previously published results and provides updated constraints on the planetary parameters. Our data are also consistent with previous transit observations of this system. The physical properties of the transiting system can only be constrained as well as the host star is characterized, so we provide new spectroscopic measurements of GJ 3470 from 0.33 to 2.42 μm to aid our analysis. We find R* = 0.48 ± 0.04 R⊙, M* = 0.51 ± 0.06 M⊙, and T_(eff) = 3652 ± 50K for GJ 3470, along with a rotation period of 20.70 ± 0.15 d and an R-band amplitude of 0.01 mag, which is small enough that current transit measurements should not be strongly affected by stellar variability. However, to report definitively whether stellar activity has a significant effect on the light curves, this requires future multiwavelength, multi-epoch studies of GJ 3470. We also present the most precise orbital ephemeris for this system: To = 2455983.70472 ± 0.00021BJD_(TDB), P = 3.336 6487^(+0.0000043)_(−0.0000033)  d, and we see no evidence for transit timing variations greater than 1 min. Our reported planet to star radius ratio is 0.076 42 ± 0.000 37. The physical parameters of this planet are R_p = 3.88 ± 0.32 R⊕ and M_p = 13.73 ± 1.61 M⊕. Because of our revised stellar parameters, the planetary radius we present is smaller than previously reported values. We also perform a second analysis of the transmission spectrum of the entire ensemble of transit observations to date, supporting the existence of an H_2-dominated atmosphere exhibiting a strong Rayleigh scattering slope

Divergent Chemical Cues Elicit Seed Collecting by Ants in an Obligate Multi-Species Mutualism in Lowland Amazonia

In lowland Amazonian rainforests, specific ants collect seeds of several plant species and cultivate them in arboreal carton nests, forming species-specific symbioses called ant-gardens (AGs). In this obligate mutualism, ants depend on the plants for nest stability and the plants depend on ant nests for substrate and nutrients. AG ants and plants are abundant, dominant members of lowland Amazonian ecosystems, but the cues ants use to recognize the seeds are poorly understood. To address the chemical basis of the ant-seed interaction, we surveyed seed chemistry in nine AG species and eight non-AG congeners. We detected seven phenolic and terpenoid volatiles common to seeds of all or most of the AG species, but a blend of the shared compounds was not attractive to the AG ant Camponotus femoratus. We also analyzed seeds of three AG species (Anthurium gracile, Codonanthe uleana, and Peperomia macrostachya) using behavior-guided fractionation. At least one chromatographic fraction of each seed extract elicited retrieval behavior in C. femoratus, but the active fractions of the three plant species differed in polarity and chemical composition, indicating that shared compounds alone did not explain seed-carrying behavior. We suggest that the various AG seed species must elicit seed-carrying with different chemical cues

Career Resourcing and the Process of Professional Emergence

We theorize a career resourcing process that explains how individuals can create a new profession. Using historical archives, we trace the emergence of health services research as a new research profession through the career actions of early practitioners. We find that career resourcing can lead to the institutionalization of a new profession by: 1) a process of accretion, where people pursuing fulfilling careers generate resources that contribute to institutionalization, or 2) institutional work to deliberately build the professional community and infrastructure. We contribute to research on institutional change by specifying career actions that can lead to the institutionalization of a new profession, and by developing theory that accounts for the motivations and the means of individuals to act in ways that result in the institutionalization of a new profession