Local infectious disease experience influences vaccine refusal rates: a natural experiment.

Vaccination has been critical to the decline in infectious disease prevalence in recent centuries. Nonetheless, vaccine refusal has increased in recent years, with complacency associated with reductions in disease prevalence highlighted as an important contributor. We exploit a natural experiment in Glasgow at the beginning of the twentieth century to investigate whether prior local experience of an infectious disease matters for vaccination decisions. Our study is based on smallpox surveillance data and administrative records of parental refusal to vaccinate their infants. We analyse variation between administrative units of Glasgow in cases and deaths from smallpox during two epidemics over the period 1900-1904, and vaccine refusal following its legalization in Scotland in 1907 after a long period of compulsory vaccination. We find that lower local disease incidence and mortality during the epidemics were associated with higher rates of subsequent vaccine refusal. This finding indicates that complacency influenced vaccination decisions in periods of higher infectious disease risk, responding to local prior experience of the relevant disease, and has not emerged solely in the context of the generally low levels of infectious disease risk of recent decades. These results suggest that vaccine delivery strategies may benefit from information on local variation in incidence.

Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting.

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK-wide retrospective study of 99 SCT-naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed. The median age was 32 years. Most had nodular sclerosis subtype, Eastern Cooperative Oncology Group performance status 0-1 and advanced stage disease. The median progression-free survival (PFS) was 5·6 months and median overall survival (OS) was 37·2 months. The overall response rate was 56% (29% complete response; 27% partial response). 61% reached SCT: 34% immediately post-BV and 27% following an inadequate BV response but were salvaged and underwent deferred SCT. Patients consolidated with SCT had a superior PFS and OS to those not receiving SCT (P < 0·001). BV is an effective, non-toxic bridge to immediate SCT in 34% and deferred SCT in 27%. 39% never reached SCT with a PFS of 3·0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT post-BV.

Application of the 2011 international consensus cancer cachexia classification in routine oncology dietetic practice: An observational study.

BACKGROUND: Cancer cachexia (CC) is highly prevalent and associated with significant morbidity and mortality, yet underrecognized. In 2011, an international cachexia consensus (ICC) proposed a definition, assessment framework, and stages for classification: cancer precachexia, cachexia, and refractory cachexia. The authors anticipated that a "more practical classification approach for clinical practice" would be required, which we interpreted as a bedside assessment based on clinical data. We investigated whether the ICC classification could be employed in routine dietetic practice without access to objective muscle mass measures. METHODS: Data from 200 consecutive patients with solid tumors were collected as part of clinical practice by oncology dietitians in five tertiary referral hospitals. Dietitians used information gathered during their routine assessment and applied the ICC framework to assign a stage. When the dietitian was unable to assign a stage, the reason was noted. RESULTS: Based on available data, classification was possible in 177 (88%); 23 (12%) could not be staged. The reasons cited were as follows: unknown C-reactive protein (n = 14), complex clinical situation (n = 5), unknown weight loss (n = 2), and acute illness (n = 2). Thirty (17%) of the 177 participants were judged to be noncachectic.  One hundred twelve (83%) met the criteria for 1 of the 3 ICC stages: 92 (52%) were cachectic; 35 (20%) precachectic, and 20 (11%) refractory. CONCLUSIONS: CC staging based on the ICC classification was feasible and practical in routine dietetic practice even without access to objective muscle mass measures. Once validated and operationalized, expert clinical assessment by a dietitian could be a cost-effective means to identify and stage CC, with more resource-intensive means used when there is clinical doubt.

Assimilation of elements and digestion in grass shrimp pre-exposed to dietary mercury.

Grass shrimp Palaemonetes pugio were fed mercury (Hg)-contaminated oligochaetes for 15 days and analyzed for Hg, cadmium (Cd), and carbon assimilation efficiencies (AE) as well as toxicological end points related to digestion. Disproportionate increases in stable Hg concentrations in shrimp did not appear to be related to partitioning to trophically available Hg in worms. Hg AE by pre-exposed shrimp reached a plateau (approximately 53 %), whereas Cd AE varied (approximately 40-60 %) in a manner that was not dose-dependent. Carbon AE did not differ among treatments (approximately 69 %). Gut residence time was not impacted significantly by Hg pre-exposure (grand median approximately 465 min), however, there was a trend between curves showing percentages of individuals with markers in feces over time versus treatment. Feces-elimination rate did not vary with dietary pre-exposure. Extracellular protease activity varied approximately 1.9-fold but did not exhibit dose-dependency. pH increased over the range of Hg pre-exposures within the anterior (pH approximately 5.33-6.51) and posterior (pH approximately 5.29-6.25) regions of the cardiac proventriculus and Hg assimilation exhibited a negative relationship to hydrogen ion concentrations. The results of this study indicate that previous Hg ingestion can elicit post-assimilatory impacts on grass shrimp digestive physiology, which may, in turn, influence Hg assimilation during subsequent digestive cycles.

Carbon assimilation and digestive toxicity in naïve grass shrimp (Palaemonetes pugio) exposed to dietary cadmium.

Naïve grass shrimp Palaemonetes pugio were pulse-fed cadmium-contaminated meals containing carbon-14, fluorescent or near-infrared markers and analyzed for carbon assimilation efficiency, gut residence time, feces elimination rate, extracellular digestive protease activity or gut pH. Carbon assimilation efficiency (~83%), minimum gut residence time (~435 min) and proventriculus pH (~5.29 to ~6.01) were not impacted significantly by cadmium ingestion. A dose-dependent decrease in feces elimination rate (from ~14.4 to ~6.4 mm h(-1)) was observed for shrimp for 2 h following minimum gut residence time. Protease activities increased ~2.4-fold over the range of dietary cadmium exposures, however, this variation was not dose-dependent. Differential impacts of cadmium exposure on carbon and cadmium assimilation reported previously are consistent with work involving shrimp subjected to chronic field exposure. The influence of ingested cadmium on feces elimination rate may be related to pre-assimilatory impacts on packaging, intestinal transport or release of feces. Protease activities may have been influenced by pre-assimilatory interactions between available cadmium ions in gut fluid and enzyme-secreting cells of the hepatopancreatic epithelium or direct impacts on active enzymes.

Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease.

OBJECTIVE: Variant Creutzfeldt-Jakob disease (vCJD), a novel form of human prion disease, was recognized in 1996. The disease affected a younger cohort than sporadic CJD, and the early clinical course was dominated by psychiatric and sensory symptoms. In an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. These were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. Since then, only minor changes have been introduced; revalidation of the criteria in the current format is overdue. METHODS: Included in this study are autopsy/cerebral biopsy-proven cases of vCJD referred to the National CJD Surveillance Unit (NCJDSU) between 1995 and 2004 and suspect cases in which an alternative diagnosis was identified following autopsy/cerebral biopsy. RESULTS: Over the 10-year period, 106 definite cases of vCJD and 45 pathologically confirmed "noncases" were identified from the archives of the NCJDSU. The median age at onset of the cases was significantly younger than that of the noncases (27 years [range, 12-74 years] vs 43 years [range, 10-64 years]), and the median duration of illness was significantly shorter (14 months [range, 6-39 months] vs 22 months [range, 2-139 months]). The most commonly identified core clinical feature in cases was dementia; persistent painful sensory symptoms were the least frequent. Eighty-eight of 106 (83%) vCJD cases were retrospectively classified as probable in life, 6 cases were classified as possible. Most cases were classified as probable on the basis of core clinical features and brain magnetic resonance imaging. To date, the diagnostic criteria remain 100% specific, with no autopsy/cerebral biopsy-proven noncases classified as probable in life. INTERPRETATION: This study confirms that the diagnostic criteria for vCJD are sensitive and specific and provide a useful standard framework for case classification in a surveillance setting.

Diet and Nutrition Advice After a Solid Tumor Diagnosis.

PURPOSE: Credible evidence-based diet and nutrition advice is essential for patients with cancer. This study aimed to explore what advice patients with cancer obtained before a formal dietetic visit. METHODS: A multicenter, observational study was conducted in seven hospital-based oncology services. Consecutive patients were recruited at first dietetic assessment. In addition to routine dietetic assessment, participants completed a four-item questionnaire describing diet and nutrition advice obtained since diagnosis. RESULTS: Seventy-seven patients participated. More than 80% had multiple nutrition-impact symptoms. In total, 53 (69%) obtained advice from professional and nonprofessional sources before dietetic visit. Family and friends were the most common sources of advice. More than one third got advice from (nondietetic) healthcare professionals. Most advice related to "foods to include" (61%) and "foods to avoid" (54%) in the diet. Many of the "foods to avoid" were important sources of micro- and macronutrients. Advice about dietary supplements (31%) and specific diets (28%) was common, rarely evidence-based, and frequently contradictory. Participants found it difficult to discern what advice was trustworthy and reliable. Despite this, most followed the advice. CONCLUSION: The majority of patients received diet and nutrition advice before first dietetic visit. Most of this came from nonprofessional sources. Any advice from nondietetic healthcare professionals was inconsistent or vague. This was mainly related to the avoidance and/or inclusion of particular foods and was often contradictory. Nevertheless, patients usually followed such advice fully. To help manage their frequent nutrition-impact symptoms and resolve the contradictory advice they had received, many expressed the need for earlier professional dietetic consultation.

Decadal changes in zooplankton abundance and phenology of Long Island Sound reflect interacting changes in temperature and community composition.

Between 1939 and 1982, several surveys indicated that zooplankton in Long Island Sound, NY (LIS) appeared to follow an annual cycle typical of the Mid-Atlantic coast of North America. Abundance peaked in both early spring and late summer and the peaks were similar in magnitude. In recent decades, this cycle appeared to have shifted. Only one large peak tended to occur, and summer copepod abundance was consistently reduced by ∼60% from 1939 to 1982 levels. In other Mid-Atlantic coastal systems such a dramatic shift has been attributed to the earlier appearance of ctenophores, particularly Mnemiopsis leidyi, during warmer spring months. However, over a decade of surveys in LIS have consistently found near-zero values in M. leidyi biomass during spring months. Our multiple linear regression model indicates that summer M. leidyi biomass during this decade explains <25% of the variation in summer copepod abundance. During these recent, warmer years, summer copepod community shifts appear to explain the loss of copepod abundance. Although Acartia tonsa in 2010-2011 appeared to be present all year long, it was no longer the dominant summer zooplankton species. Warmer summers have been associated with an increase in cyanobacteria and flagellates, which are not consumed efficiently by A. tonsa. This suggests that in warming coastal systems multiple environmental and biological factors interact and likely underlie dramatic alterations to copepod phenology, not single causes.

Linking the distribution of (210)Po and (210)Pb with plankton community along Line P, Northeast Subarctic Pacific.

Depth profiles of (210)Po and (210)Pb activity and phytoplankton and zooplankton abundance were collected during two cruises along the Canadian time-series Line P in the Northeast Subarctic Pacific (ranging from 48o39 N to 50o00 N and 126o40 W to 145o00 W) in August 2010 and February 2011 to evaluate connections between the planktonic community and distributions of these radionuclides in the upper 500 m of the water column. Statistical analysis indicates that (210)Po is more effectively removed from the surface ocean when large (>0.1 mg ind(-1) dry wt) zooplankton dominate, and is less effectively scavenged when the picoplankton Synechococcus is present at high concentrations (>1 × 10(5) cells ml(-1)). While the zooplankton field data are consistent with previous lab studies and field observations, the phytoplankton results seem to conflict with recent evidence that small cells may contribute significantly to export in other oligotrophic regions. Differences in ecosystem mechanisms between the Subarctic Pacific and other oligotrophic systems that limit the contribution of small cells to sinking flux remain to be identified.

Direct comparison of 210Po, 234Th and POC particle-size distributions and export fluxes at the Bermuda Atlantic Time-series Study (BATS) site.

Particle-reactive, naturally occurring radionuclides are useful tracers of the sinking flux of organic matter from the surface to the deep ocean. Since the Joint Global Ocean Flux Study (JGOFS) began in 1987, the disequilibrium between (234)Th and its parent (238)U has become widely used as a technique to measure particle export fluxes from surface ocean waters. Another radionuclide pair, (210)Po and (210)Pb, can be used for the same purpose but has not been as widely adopted due to difficulty with accurately constraining the (210)Po/(210)Pb radiochemical balance in the ocean and because of the more time-consuming radiochemical procedures. Direct comparison of particle flux estimated in different ocean regions using these short-lived radionuclides is important in evaluating their utility and accuracy as tracers of particle flux. In this paper, we present paired (234)Th/(238)U and (210)Po/(210)Pb data from oligotrophic surface waters of the subtropical Northwest Atlantic and discuss their advantages and limitations. Vertical profiles of total and particle size-fractionated (210)Po and (234)Th activities, together with particulate organic carbon (POC) concentrations, were measured during three seasons at the Bermuda Atlantic Time-series Study (BATS) site. Both (210)Po and (234)Th reasonably predict sinking POC flux caught in sediment traps, and each tracer provides unique information about the magnitude and efficiency of the ocean's biological pump.