High dimensional mediation analysis with latent variables

We propose a model for high dimensional mediation analysis that includes latent variables. We describe our model in the context of an epidemiologic study for incident breast cancer with one exposure and a large number of biomarkers (i.e., potential mediators). We assume that the exposure directly influences a group of latent, or unmeasured, factors which are associated with both the outcome and a subset of the biomarkers. The biomarkers associated with the latent factors linking the exposure to the outcome are considered “mediators.” We derive the likelihood for this model and develop an expectation‐maximization algorithm to maximize an L1‐penalized version of this likelihood to limit the number of factors and associated biomarkers. We show that the resulting estimates are consistent and that the estimates of the nonzero parameters have an asymptotically normal distribution. In simulations, procedures based on this new model can have significantly higher power for detecting the mediating biomarkers compared with the simpler approaches. We apply our method to a study that evaluates the relationship between body mass index, 481 metabolic measurements, and estrogen‐receptor positive breast cancer.     

Towards an urban marine ecology: characterizing the drivers,patterns and processes of marine ecosystems in coastal cities

Human population density within 100 km of the sea is approximately three times higher than the global average. People in this zone are concentrated in coastal cities that are hubs for transport and trade – which transform the marine environment. Here, we review the impacts of three interacting drivers of marine urbanization (resource exploitation, pollution pathways and ocean sprawl) and discuss key characteristics that are symptomatic of urban marine ecosystems. Current evidence suggests these systems comprise spatially heterogeneous mosaics with respect to artificial structures, pollutants and community composition, while also undergoing biotic homogenization over time. Urban marine ecosystem dynamics are often influenced by several commonly observed patterns and processes, including the loss of foundation species, changes in biodiversity and productivity, and the establishment of ruderal species, synanthropes and novel assemblages. We discuss potential urban acclimatization and adaptation among marine taxa, interactive effects of climate change and marine urbanization, and ecological engineering strategies for enhancing urban marine ecosystems. By assimilating research findings across disparate disciplines, we aim to build the groundwork for urban marine ecology – a nascent field; we also discuss research challenges and future directions for this new field as it advances and matures. Ultimately, all sides of coastal city design: architecture, urban planning and civil and municipal engineering, will need to prioritize the marine environment if negative effects of urbanization are to be minimized. In particular, planning strategies that account for the interactive effects of urban drivers and accommodate complex system dynamics could enhance the ecological and human functions of future urban marine ecosystems.     

Phytoplankton countings. Intercalibration results and recommendations for routine work

Intercalibrations of phytoplankton countings were made in the Baltic in 1974 and 1975, where seven laboratories participated, each using their routine method. A statistical evaluation was made on the results, and recommendations for routine countings with the Utermöhl technique are given.     

Nerves on tr[ac]k to support pancreatic cancer metabolism

Nerve-cancer interactions modulate pancreatic cancer growth through direct effects on cancer cells and the microenviron-ment.New evidence now shows that nerves ...     

Ultrastructure of spermiogenesis in the American alligator,Alligator mississippiensis (Reptilia,Crocodylia, Alligatoridae)

Testicular samples were collected to describe the ultrastructure of spermiogenisis in Alligator mississipiensis (American Alligator). Spermiogenesis commences with an acrosome vesicle forming from Golgi transport vesicles. An acrosome granule forms during vesicle contact with the nucleus, and remains posterior until mid to late elongation when it diffuses uniformly throughout the acrosomal lumen. The nucleus has uniform diffuse chromatin with small indices of heterochromatin, and the condensation of DNA is granular. The subacrosome space develops early, enlarges during elongation, and accumulates a thick layer of dark staining granules. Once the acrosome has completed its development, the nucleus of the early elongating spermatid becomes associated with the cell membrane flattening the acrosome vesicle on the apical surface of the nucleus, which aids in the migration of the acrosomal shoulders laterally. One endonuclear canal is present where the perforatorium resides. A prominent longitudinal manchette is associated with the nuclei of late elongating spermatids, and less numerous circular microtubules are observed close to the acrosome complex. The microtubule doublets of the midpiece axoneme are surrounded by a layer of dense staining granular material. The mitochondria of the midpiece abut the proximal centriole resulting in a very short neck region, and possess tubular cristae internally and concentric layers of cristae superficially. A fibrous sheath surrounds only the axoneme of the principal piece. Characters not previously described during spermiogenesis in any other amniote are observed and include (1) an endoplasmic reticulum cap during early acrosome development, (2) a concentric ring of endoplasmic reticulum around the nucleus of early to middle elongating spermatids, (3) a band of endoplasmic reticulum around the acrosome complex of late developing elongate spermatids, and (4) midpiece mitochondria that have both tubular and concentric layers of cristae. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.     

Gene mapping by linkage and association analysis

Genetic analysis is used to map genes, including disease loci, to positions within the human genome. Linkage analysis depends on the co-segregation of a gene (locus) and a phenotype through a pedigree, while association analysis, or linkage disequilibrium mapping, depends on measuring deviation from the random occurrence of alleles in a haplotype in unrelated individuals or nuclear families. Complex computer programs may be used in both forms of analysis. In recent years most interest has focused on identifying genes involved in common, multifactorial diseases. Here I review some current and developing techniques of genetic analysis and give references to where further information can be obtained.     

Perinatal mortality and morbidity among babies delivered in water: surveillance study and postal survey

AimTo compare perinatal morbidity and mortality for babies delivered in water with rates for babies delivered conventionally (not in water).DesignSurveillance study (of all consultant paediatricians) and postal survey (of all NHS maternity units).SettingBritish Isles (surveillance study); England and Wales (postal survey).SubjectsBabies born in the British Isles between April 1994 and March 1996 who died perinatally or were admitted for special care within 48 hours of birth after delivery in water or after labour in water followed by conventional delivery (surveillance study); babies delivered in water in England and Wales in the same period (postal survey).Results4032 deliveries (0.6% of all deliveries) in England and Wales occurred in water. Perinatal mortality was 1.2/1000 (95% confidence interval 0.4 to 2.9) live births; 8.4/1000 (5.8 to 11.8) live births were admitted for special care. No deaths were directly attributable to delivery in water, but 2 admissions were for water aspiration. UK reports of mortality and special care admission rates for babies of women considered to be at low risk of complications during delivery who delivered conventionally ranged from 0.8/1000 (0.2 to 4.2) to 4.6/1000 (0.1 to 25) live births and from 9.2 (1.1 to 33) to 64/1000 (58 to 70) live births respectively. Compared with regional data for low risk, spontaneous, normal vaginal deliveries at term, the relative risk for perinatal mortality associated with delivery in water was 0.9 (99% confidence interval 0.2 to 3.6).ConclusionsPerinatal mortality is not substantially higher among babies delivered in water than among those born to low risk women who delivered conventionally. The data are compatible with a small increase or decrease in perinatal mortality for babies delivered in water.

Key messages

• Data on adverse effects of delivery in water have been limited
• Perinatal mortality and risk of admission for special care is similar for babies delivered in water and for low risk deliveries that do not take place in water
• The risk of perinatal mortality for babies delivered in water is similar to the risk for babies born by normal vaginal delivery to women at low risk of adverse outcome
• Delivery in water may have caused water aspiration in two babies and contributed to snapped umbilical cord in five