Calibration of a high spectral resolution lidar using a Michelson interferometer, with data examples from ORACLES.

The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.

A multicentre snapshot study of the incidence of serious procedural complications secondary to central venous catheterisation.

Despite the high number of central venous access devices inserted annually, there are limited data on the incidence of the associated procedural complications, many of which carry substantial clinical risk. This point was highlighted in the recently published Association of Anaesthetists of Great Britain and Ireland 'Safe vascular access 2016' guidelines. This trainee-led snapshot study aimed to identify the number of central venous catheter insertions and the incidence of serious complications across multiple hospital sites within a fixed two-week period. Secondary aims were to identify the availability of resources and infrastructure to facilitate safe central venous catheter insertion and management of potential complications. Fifteen hospital sites participated, completing an initial resource survey and daily identification of all adult central venous catheter insertions, with subsequent review of any complications detected. A total of 487 central venous catheter insertions were identified, of which 15 (3.1%) were associated with a significant procedural complication. The most common complication was failure of insertion, which occurred in seven (1.4%) cases. Facilities to enable safer central venous catheter insertion and manage complications varied widely between hospitals, with little evidence of standardisation of guidelines or protocols.

Combined use of bacteriophage K and a novel bacteriophage to reduce Staphylococcus aureus biofilm formation.

Biofilms are major causes of impairment of wound healing and patient morbidity. One of the most common and aggressive wound pathogens is Staphylococcus aureus, displaying a large repertoire of virulence factors and commonly reduced susceptibility to antibiotics, such as the spread of methicillin-resistant S. aureus (MRSA). Bacteriophages are obligate parasites of bacteria. They multiply intracellularly and lyse their bacterial host, releasing their progeny. We isolated a novel phage, DRA88, which has a broad host range among S. aureus bacteria. Morphologically, the phage belongs to the Myoviridae family and comprises a large double-stranded DNA (dsDNA) genome of 141,907 bp. DRA88 was mixed with phage K to produce a high-titer mixture that showed strong lytic activity against a wide range of S. aureus isolates, including representatives of the major international MRSA clones and coagulase-negative Staphylococcus. Its efficacy was assessed both in planktonic cultures and when treating established biofilms produced by three different biofilm-producing S. aureus isolates. A significant reduction of biofilm biomass over 48 h of treatment was recorded in all cases. The phage mixture may form the basis of an effective treatment for infections caused by S. aureus biofilms.

The genome of the simian and human malaria parasite Plasmodium knowlesi.

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.

Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.

PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design. Each cohort included three healthy subjects (PRM-151:placebo; 2:1). SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP. At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients. In addition, the percentage of fibrocytes (CD45+/Procollagen-1+ cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population. PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30 h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.

De-medicalising public mental health with the Power Threat Meaning Framework.

AIMS: To propose that the language and concepts in public mental health are often medicalised and to suggest that the power threat meaning framework (PTMF), can be a useful resource for those wishing to take a de-medicalising approach. METHOD: Examples of medicalisation from the literature and from practice are discussed and key constructs in the PTMF are explained, drawing from the report which presented its research base. RESULTS: Examples of medicalisation in public mental health include: the uncritical use of psychiatric diagnostic categories; the 'illness like any other' approach in anti-stigma campaigns; and the implicit privileging of biology in the biopsychosocial model. The negative operations of power in society are seen as posing threats to human needs and people make sense of such situations in varied ways, though there are some commonalities. This gives rise to culturally available and bodily enabled threat responses which serve a variety of functions. From a medicalised perspective, these responses to threat are characteristically seen as 'symptoms' of underlying disorders. The PTMF is both a conceptual framework and a practical tool that can be used by individuals, groups and communities. CONCLUSION: Consistent with social epidemiological research, prevention efforts should focus on preventing adversity rather than 'disorders' but the added value of the PTMF is that varied problems can be understood in an integrated manner as responses to a variety of threats whose functions could be met in different ways. Its message that mental distress is often a response to adversity is comprehensible to the public and can be communicated in an accessible way.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task.

The current study used the partially-baited radial-arm maze paradigm to study the effects of a single-treatment high-dose exposure ('binge') to MDMA (± 3,4-methylenedioxymethaphemtamine or 'Ecstasy') on memory task acquisition. Sprague-Dawley rats were administered a binge dose (4 × 10 mg/kg) of MDMA and their ability to subsequently acquire the radial-arm maze task was compared against saline controls. The MDMA-treated rats were significantly slower to learn the task and made more reference memory errors than the controls. Working memory function was found to be relatively unimpaired. Following a reversal of task rules the MDMA-treated rats were again significantly slower to acquire the appropriate rule despite having eventually achieved a similar level of overall performance as control rats. However evidence of drug tolerance was found when all rats were challenged with an acute low dose of MDMA (1 × 4.0 mg/kg) because the binge MDMA rats were relatively less impaired. Therefore, although binge treated MDMA rats were able to achieve very accurate performance equivalent to the controls they took significantly longer to do this and were less able to adapt their behavior to a change in task rules. In addition the binge treated MDMA rats displayed tolerance to acute MDMA exposure. These findings are consistent with the possibility that human Ecstasy users may show deficits in acquiring information and may experience deficits in cognitive flexibility as well as developing tolerance to the drug with repeated exposure.

Bacteriophages for the treatment of Pseudomonas aeruginosa infections.

Bacteriophages were first identified in 1915 and were used as antimicrobial agents from 1919 onwards. Despite apparent successes and widespread application, early users did not understand the nature of these agents and their efficacy remained controversial. As a result, they were replaced in the west by chemical antibiotics once these became available. However, bacteriophages remained a common therapeutic approach in parts of Eastern Europe where they are still in use. Increasing levels of antibiotic-resistant bacterial infections are now driving demand for novel therapeutic approaches. In cases where antibiotic options are limited or nonexistent, the pressure for new agents is greatest. One of the most prominent areas of concern is multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa is a prominent member of this class and is the cause of damaging infections that can be resistant to successful treatment with conventional antibiotics. At the same time, it exhibits a number of properties that make it a suitable target for bacteriophage-based approaches, including growth in biofilms that can hydrolyse following phage infection. Pseudomonas aeruginosa provides a striking example of an infection where clinical need and the availability of a practical therapy coincide.

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

Grey hair: clinical investigation into changes in hair fibres with loss of pigmentation in a photoprotected population.

Loss of pigmentation in hair fibres is one of the most obvious phenotypic changes with ageing and has been a topic of increasing interest in the study of follicle biology. The onset of greying brings cosmetic complaints that grey fibres are wild or difficult to manage. Of course, these perceptions may be the consequence of visual obviousness rather than underlying physical or chemical differences. Although several studies have compared pigmented and unpigmented fibres, few have tried to control genetic and ethnic difference as well as extrinsic factors such as photoexposure and chemical treatment. We have recruited subjects with salt-and-pepper hair from a population of Old Order Mennonites who, for cultural reasons, are not only prohibited from chemically treating their hair but also limit their exposure to sunlight. Hair samples were examined for elemental composition, surface energy, Young's modulus, break stress, bending modulus, shear modulus and water sorption/desorption isotherm. The parameters were evaluated statistically for global differences, individual differences and typical individual differences. Consistent with previous published literature, few global differences were found between pigmented and unpigmented hair across the population. We do find that many individual subjects had differences between pigmented and unpigmented fibres. These differences tend to be more pronounced in bulk than in surface properties. The small differences in mechanical properties and moisture uptake and loss lend support to the perception by consumers that grey hair is wilder, drier and less manageable.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Differential effects of MDMA and scopolamine on working versus reference memory in the radial arm maze task.

Previous research has suggested that the disruption to memory-task performance seen following acute exposure to 3,4-methylenedioxymethaphemtamine (MDMA) with rats might best be characterized as reference memory impairment rather than a working memory impairment. The current study specifically compared the effects of MDMA and scopolamine on measures of working versus reference memory in an eight-arm radial maze task. It was predicted that scopolamine would produce a greater impairment with respect to the working memory component of the task, whereas MDMA would produce a greater impairment to reference memory. On each trial rats were allowed to make a total of four arm visits in order to collect the reinforcers located at the end of different arms in the maze. Working memory errors were indicated by re-visiting an already visited arm during a trial, whereas visiting an arm that was never baited on any trial indicated a reference memory error. Using a within subjects design, rats were exposed to a range of doses of scopolamine and MDMA administered acutely. An interaction between drug type and memory error type was found. Specifically, scopolamine produced more working memory errors than reference memory errors, while MDMA produced the opposite pattern of significantly more reference memory errors compared to working memory error. This finding supported the hypothesis that MDMA disrupts reference memory processes in terms of an impairment in the strategies or rules used for solving memory tasks.

Bacteriophage applications: where are we now?

Bacteriophages are bacterial viruses and have been used for almost a century as antimicrobial agents. In the West, their use diminished when chemical antibiotics were introduced, but they remain a common therapeutic approach in parts of eastern Europe. Increasing antibiotic resistance in bacteria has driven the demand for novel therapies to control infections and led to the replacement of antibiotics in animal husbandry. Alongside this, increased pressure to improve food safety has created a need for faster detection of pathogenic bacteria. Hence, there has been a resurgence of interest in bacteriophage applications, and this has encouraged the emergence of a large number of biotech companies hoping to commercialize their use. Research in Europe and the United States has increased steadily, leading to the development of a range of applications for bacteriophage agents for the healthcare, veterinary and agricultural sectors. This article will attempt to answer the question of whether bacteriophages are now delivering on their potential.

Dissolved organic matter in a tropical saline-alkaline lake of the East African Rift Valley.

Saline-alkaline lakes of the East African Rift are known to have an extremely high primary production supporting a potent carbon cycle. To date, a full description of carbon pools in these lakes is still missing. More specifically, there is not detailed information on the quality of dissolved organic matter (DOM), the main carbon energy source for heterotrophs prokaryotes. We report the first exhaustive description of DOM molecular properties in the water column of a meromictic saline-alkaline lake of the East African Rift. DOM availability, fate and origin were studied either quantitatively, in terms of dissolved organic carbon (DOC) and nitrogen (DON) or qualitatively, in terms of optical properties (absorbance) and molecular characterization of solid-phase extracted DOM (SPE-DOM) through negative electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). DOM availability was high (DOC ∼ 8.1 mM in surface waters) and meromixis imprinted a severe quantitative and qualitative change on DOM pool. At the surface, DOM was rich in aliphatic and moderately in aromatic molecules and thus mirroring autochthonous microbial production together with photodegradation. At the bottom changes were extreme: DOC increased up to 5 times (up to 50 mM) and, molecular signature drifted to saturated, reduced and non-aromatic DOM suggesting intense microbial activity within organic sediments. At the chemocline, DOC was retained indicating that this interface is a highly reactive layer in terms of DOM processing. These findings underline that saline-alkaline lakes of the East African Rift are carbon processing hot spots and their investigation may broaden our understanding of carbon cycling in inland waters at large.

Visual effects of auditory deprivation: common intermodal and intramodal factors.

Visual temporal acuity, as measured by the critical flicker frequency decreased and then increased during 24 hours of auditory deprivation. This intermodal effect is similar to intramodal changes in the critical flicker frequency of the nonoccluded eye during monocular deprivation; a single mechanism appears to underlie both phenomena.

Ligula intestinalis (Cestoda: Diphyllobothriidae) in Kenya: a field investigation into host specificity and behavioural alterations.

Within the distribution of Ligula intestinalis, a tapeworm affecting freshwater fishes, there are genetically distinct and well-separated phylogenetic clusters. East Africa is represented by a single monophyletic clade which is understudied compared with Euro-Mediterranean clades. The present field investigation in the Lake Baringo and Naivasha catchments, Kenya, revealed that this L. intestinalis clade was highly host-specific, present in only 2 of 12 fishes examined; Barbus paludinosus in Naivasha and Barbus lineomaculatus in Baringo. In infected fish, cestodes comprised up to 20% of body weight. Only 1 parasite was recorded per fish, a contrast to infected fishes in Europe where mixed infections are commonplace. In B. lineomaculatus in Baringo, only fish of greater than 64 mm in length were parasitized. The highest parasite prevalence was recorded in fish of 70-77 mm in length, and reduced for lengths of 78-84 mm. Parasitized fish were significantly associated with a particular type of habitat, occurring most frequently in shallow littoral areas, and being absent from open water and rocky shore habitats. Uninfected fish were present in all habitats. This relationship between spatial occupancy and parasite prevalence is suggested to arise from behavioural alterations induced by the parasite that promotes completion of the parasite life cycle.

A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.

OBJECTIVES: To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis. DESIGN: Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process. SETTING: A single specialist university hospital. PARTICIPANTS: 24 patients with chronic otitis with a duration of several years (2-58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured. MAIN OUTCOME MEASURES: Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only. RESULTS: Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported. CONCLUSION: The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.

Science into policy: preparing for pandemic influenza.

Authoratative government pandemic preparedness requires an evidence-based approach. The scientific advisory process that has informed the current UK pandemic preparedness plans is described. The final endorsed scientific papers are now publicly available.

Effects of acclimation on the toxicity of stream water contaminated with zinc and cadmium to juvenile cutthroat trout.

We investigated the influence of acclimation on results of in situ bioassays with cutthroat trout in metal-contaminated streams. Cutthroat trout (Oncorhynchus clarki) were held for 21 days (1) in live containers at a reference or "clean" site having dissolved metals near detection limits (0.01 microg/L cadmium [Cd] and 2.8 microg/L zinc [Zn]; hardness 32 mg/L as CaCO(3)) and (2) at a site in a mining-impacted watershed having moderately increased metals (0.07 microg/L Cd and 38 to 40 microg/L Zn; hardness 50 mg/L as CaCO(3)). The 96-hour survival of each treatment group was then tested in situ at five sites from September 5 to 9, 2002, and each group exhibited a range of metal concentrations (0.44 to 39 microg/L arsenic [As], 0.01 to 2.2 microg/L Cd, and 0.49 to 856 microg/L Zn). Survival was 100% at three sites for both treatments. However, a higher percentage of metal-acclimated fish survived at the site with the second highest concentrations of Cd and Zn (0.90 and 238 microg/L, respectively) compared with fish acclimated at the reference site (100% vs. 55%, respectively). Survival was 65% for acclimated fish and 0% for metal-naïve fish at the site with the largest metal concentrations (2.2 microg/L Cd and 856 microg/L Zn). Water collected from the site with the largest concentrations of dissolved metals (on October 30, 2002) was used in a laboratory serial dilution to determine 96-hour LC(50) values. The 96-hour LC(50) estimates of naïve fish during the in situ and laboratory experiments were similar (0.60 mug Cd/L and 226 microg Zn/L for in situ and 0.64 microg Cd/L and 201 microg Zn/L for laboratory serial dilutions). However, mortality of naïve cutthroat trout tested under laboratory conditions was more rapid in dilutions of 100%, 75%, and 38% site water than in situ experiments.