The COSPAR planetary protection policy for missions to Icy Worlds: A review of history, current scientific knowledge, and future directions.

Recent discoveries related to the habitability and astrobiological relevance of the outer Solar System have expanded our understanding of where and how life may have originated. As a result, the Icy Worlds of the outer Solar System have become among the highest priority targets for future spacecraft missions dedicated to astrobiology-focused and/or direct life detection objectives. This, in turn, has led to a renewed interest in planetary protection concerns and policies for the exploration of these worlds and has been a topic of discussion within the COSPAR (Committee on Space Research) Panel on Planetary Protection. This paper summarizes the results of those discussions, reviewing the current knowledge and the history of planetary protection considerations for Icy Worlds as well as suggesting ways forward. Based on those discussions, we therefore suggest to (1) Establish a new definition for Icy Worlds for Planetary Protection that captures the outer Solar System moons and dwarf planets like Pluto, but excludes more primitive bodies such as comets, centaurs, and asteroids: Icy Worlds in our Solar System are defined as all bodies with an outermost layer that is believed to be greater than 50 % water ice by volume and have enough mass to assume a nearly round shape. (2) Establish indices for the lower limits of Earth life with regards to water activity (LLAw) and temperature (LLT) and apply them into all areas of the COSPAR Planetary Protection Policy. These values are currently set at 0.5 and -28 °C and were originally established for defining Mars Special Regions; (3) Establish LLT as a parameter to assign categorization for Icy Worlds missions. The suggested categorization will have a 1000-year period of biological exploration, to be applied to all Icy Worlds and not just Europa and Enceladus as is currently the case. (4) Have all missions consider the possibility of impact. Transient thermal anomalies caused by impact would be acceptable so long as there is less than 10-4 probability of a single microbe reaching deeper environments where temperature is >LLT in the period of biological exploration. (5) Restructure or remove Category II* from the policy as it becomes largely redundant with this new approach, (6) Establish that any sample return from an Icy World should be Category V restricted Earth return.

The Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part III Non-penicillin and Non-cephalosporin Drugs.

INTRODUCTION: Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that systematically reviews literature on the PK and analyzes if, based on the changed PK, evidence-based dosing regimens have been developed for adequate target attainment in pregnant women. This part focusses on antimicrobials other than penicillins and cephalosporins. METHODS: A literature search was conducted in PubMed according to the PRISMA guidelines. Search strategy, study selection, and data extraction were independently performed by two investigators. Studies were labeled as relevant when information on the PK of antimicrobial drugs in pregnant women was available. Extracted parameters included bioavailability for oral drugs, volume of distribution (Vd) and clearance (CL), trough and peak drug concentrations, time of maximum concentration, area under the curve and half-life, probability of target attainment, and minimal inhibitory concentration (MIC). In addition, if developed, evidence-based dosing regimens were also extracted. RESULTS: Of the 62 antimicrobials included in the search strategy, concentrations or PK data during pregnancy of 18 drugs were reported. Twenty-nine studies were included, of which three discussed aminoglycosides, one carbapenem, six quinolones, four glycopeptides, two rifamycines, one sulfonamide, five tuberculostatic drugs, and six others. Eleven out of 29 studies included information on both Vd and CL. For linezolid, gentamicin, tobramycin, and moxifloxacin, altered PK throughout pregnancy, especially in second and third trimester, has been reported. However, no target attainment was studied and no evidence-based dosing developed. On the other hand, the ability to reach adequate targets was assessed for vancomycin, clindamycin, rifampicin, rifapentine, ethambutol, pyrazinamide, and isoniazid. For the first six mentioned drugs, no dosage adaptations during pregnancy seem to be needed. Studies on isoniazid provide contradictory results. CONCLUSION: This systematic literature review shows that a very limited number of studies have been performed on the PK of antimicrobials drugs-other than cephalosporins and penicillins-in pregnant women.

Visual outcomes and ocular morbidity of patients with uveitis referred to a tertiary center during first year of follow-up.

PURPOSE: To describe the visual outcomes and morbidity of newly referred uveitis patients. METHODS: Retrospective cohort study of 133 newly referred uveitis patients with active uveitis who required care in a tertiary center for at least 1 year. Main outcomes were best-corrected visual acuity (BCVA) at referral and 1 year after referral, duration of visual impairment, systemic medications used, as well as all complications and surgeries during the first year of follow-up. Generalized estimating equation models was used to assess prognosticators for poor BCVA. RESULTS: The mean age at onset of uveitis was 43 years. The proportion of patients with at least one eye with BCVA ≤0.3 decreased from 35% at referral to 26% (P=0.45) at 1-year follow-up. The mean duration of visual impairment in the first year after referral was 4 months per affected eye. At 1-year follow-up, bilateral visual impairment was observed in 4% but at least one ocular complication developed in 66% and 30% of patients required at least one intraocular surgery. Systemic immunosuppressive treatment was required in 35% of patients and the mean number of visits to ophthalmologist was 11 per year, while 8% of patients required hospital admission. Prognosticators for poor visual outcome included surgery undergone before referral (odds ratio (OR), 3; 95% CI, 1-11; P=0.047), visual impairment at referral (OR, 21; 95% CI, 8-54; P<0.001), and glaucoma before referral (OR, 7; 95% CI, 2-28; P=0.007). CONCLUSIONS: Patients with severe uveitis had a favorable BCVA 1 year after referral with only 4% of patients having bilateral visual impairment. This, in contrast to the prolonged duration of visual impairment during the first year of follow-up and the demanding care.

Extension type fracture of the ankylotic thoracic spine with gross displacement causing esophageal rupture.

PURPOSE: This study aimed at discussing the relevance of the type B3 fracture of the new AOSpine classification. METHODS: Hyperextension fractures of the spine are rare in the general population, but common in the ankylotic spine. We present a case of a severe spinal fracture with concomitant esophageal rupture, which was diagnosed early and could be treated during the initial trauma care. RESULTS: The spinal column was stabilized using a percutaneous technique after which the perforated esophagus was sutured through a thoracotomy. The spinal injury was classified a type B3 fracture using the new AOSpine classification. CONCLUSION: The B3 typification raised a lot of discussion during the development of the new classification system and may be controversial. This case, however, nicely illustrates the relevance of an intact posterior hinge as compared to C-type injuries where complete dissociation is present with inherent spinal cord damage.

Functional electrical stimulation by means of the 'Ness Handmaster Orthosis' in chronic stroke patients: an exploratory study.

OBJECTIVE: To gain experience with 'Ness Handmaster Orthosis' treatment in chronic stroke patients, to identify suitable patients, and to study the effects of treatment. DESIGN: Exploratory, uncontrolled trial with measurement of motor functions and muscle tone of the upper extremity prior to, during, upon completion, and six weeks after a treatment period. SETTING: A rehabilitation centre in the Netherlands. SUBJECTS: Eighteen chronic stroke patients (more than six months post stroke), who exhibited upper extremity dysfunction due to spastic paresis. INTERVENTION: A 10-week therapy programme of functional electrical stimulation by means of the 'Ness Handmaster Orthosis'. RESULTS: The results of 15 patients were available for analysis. The differences in motor score and muscle tone before and at the end of treatment were statistically significant (p = 0.008 and 0.021, respectively). The follow-up measurements showed that the effects on motor functions and muscle tone decreased after therapy completion. Stratification of the patients in two subgroups indicated that patients with initial high motor scores benefited most during the intervention period. CONCLUSION: The present study suggests that Handmaster treatment possesses therapeutic opportunities in chronic stroke patients with spastic paresis of the upper extremity.

Use of the NESS handmaster to restore handfunction in tetraplegia: clinical experiences in ten patients.

OBJECTIVE: To explore possible functional effects of the Handmaster in tetraplegia and to determine suitable patients for the system. PATIENTS: Patients with a cervical spinal cord injury between C4 and C6, motor group 0 - 3. Important selection criteria were a stable clinical situation and the absence of other medical problems and complications. DESIGN: Ten patients were consecutively selected from the in- and outpatient department of a large rehabilitation hospital in The Netherlands. Each patient was fitted with a Handmaster by a qualified therapist and underwent muscle strength and functional training for at least 2 months. METHODS: Functional evaluation comprised the performance of a defined set of tasks and at least one additional task as selected by patients themselves. Tasks were performed both with and without the Handmaster. Finally, patients were asked for their opinion on Handmaster use as well as their willingness to future use. RESULTS: In six patients a stimulated grasp and release with either one or both grasp modes (key- and palmar pinch) of the Handmaster was possible. Four patients could perform the set of tasks using the Handmaster, while they were not able to do so without the Handmaster. Eventually, one patient continued using the Handmaster during ADL at home. CONCLUSION: The Handmaster has a functional benefit in a limited group of patients with a C5 SCI motor group 0 and 1. Suitable patients should have sufficient shoulder and biceps function combined with absent or weak wrist extensors. Though functional use was the main reason for using the Handmaster, this case series showed that therapeutic use can also be considered.

Canada's national initiative to advance access to electronic journals.

This paper describes a national experiment in the licensing of full text information in journals, primarily in the fields of science, technology and medicine. It discusses the initiative of the federal government of Canada through the creation of the Canada Foundation for Innovation as a new funding agency, with an objective of improving research and creativity in Canadian science. The successful efforts initiated by the Canadian Association of Research Libraries/Association des bibliothèques de recherche du Canada to create a funding opportunity to develop the 'information infrastructure' for Canadian researchers and the resulting Canadian National Site Licensing Project (CNSLP) progress is discussed. The evolution of a project governance structure to maintain the support of the 64 participating institutions is reviewed and the need to develop an appropriate exit strategy at the conclusion of the federal funding is also considered.

Fin-de-siècle Philadelphia and the founding of the Medical Library Association.

Philadelphia at the time of the founding of the Medical Library Association (MLA) is described. Several factors that promoted the birth of the association are discussed, including the rapid increase in the labor force and the rise of other health related professions, such as the American Hospital Association and the professionalization of nursing. The growth of the public hygiene movement in Philadelphia at the time of Sir William Osler's residency in the city is discussed. Finally, the rapid growth of the medical literature is considered a factor promoting the development of the association. This article continues the historical consideration of the MLA begun in the author's article on the three founders of the association. The background information is drawn from the items listed in the bibliography, and the conclusions are those of the author.

Three who made an association: I. Sir William Osler, 1849-1919. II. George Milbry Gould, 1848-1922. III. Margaret Ridley Charlton, 1858-1931 and the founding of the Medical Library Association, Philadelphia, 1898.

The careers and personalities of the three founders of the Medical Library Association, Sir William Osler, George Milbry Gould, and Margaret Ridley Charlton are outlined, followed by a review of their role in the founding of the association. The career of Sir William Osler is well documented in existing literature, both in medical history and medical librarianship; the biographies of George Milbry Gould and Margaret Ridley Charlton are less known, and this article describes their lives in relation to the founding of the association. The issue of responsibility for the association's founding is explored, and primary recognition is attributed to Margaret Charlton. The author attempts to follow the tradition of Harvey Cushing in his The Life of Sir William Osler in allowing the characters to speak in their own words as much as possible.

Three who made an association: I. Sir William Osler, 1849-1919 II. George Milbry Gould, 1848-1922 III. Margaret Ridley Charlton, 1858-1931 and the founding of the Medical Library Association, Philadelphia, 1898.

The careers and personalities of the three founders of the Medical Library Association, Sir William Osler, George Milbry Gould, and Margaret Ridley Charlton are outlined, followed by a review of their role in the founding of the association. The career of Sir William Osler is well documented in existing literature, both in medical history and medical librarianship; the biographies of George Milbry Gould and Margaret Ridley Charlton are less known, and this article describes their lives in relation to the founding of the association. The issue of responsibility for the association's founding is explored, and primary recognition is attributed to Margaret Charlton. The author attempts to follow the tradition of Harvey Cushing in his The Life of Sir William Osler in allowing the characters to speak in their own words as much as possible.

Estimation of protein secondary structure and error analysis from circular dichroism spectra.

The estimation of protein secondary structure from circular dichroism spectra is described by a multivariate linear model with noise (Gauss-Markoff model). With this formalism the adequacy of the linear model is investigated, paying special attention to the estimation of the error in the secondary structure estimates. It is shown that the linear model is only adequate for the alpha-helix class. Since the failure of the linear model is most likely due to nonlinear effects, a locally linearized model is introduced. This model is combined with the selection of the estimate whose fractions of secondary structure summate to approximately one. Comparing the estimation from the CD spectra with the X-ray data (by using the data set of W.C. Johnson Jr., 1988, Annu. Rev. Biophys. Chem. 17, 145-166) the root mean square residuals are 0.09 (alpha-helix), 0.12 (anti-parallel beta-sheet), 0.08 (parallel beta-sheet), 0.07 (beta-turn), and 0.09 (other). These residuals are somewhat larger than the errors estimated from the locally linearized model. In addition to alpha-helix, in this model the beta-turn and "other" class are estimated adequately. But the estimation of the antiparallel and parallel beta-sheet class remains unsatisfactory. We compared the linear model and the locally linearized model with two other methods (S. W. Provencher and J. Glöckner, 1981, Biochemistry 20, 1085-1094; P. Manavalan and W. C. Johnson Jr., 1988, Anal. Biochem. 167, 76-85). The locally linearized model and the Provencher and Glöckner method provided the smallest residuals. However, an advantage of the locally linearized model is the estimation of the error in the secondary structure estimates.

Fentanyl pretreatment modifies anaesthetic induction with etomidate.

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I = 2 ml normal saline; Group II = 100 micrograms of fentanyl; Group III = 250 micrograms of fentanyl; Group IV = 500 micrograms of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P less than 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P less than 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 micrograms of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.