Understanding charged vesicle suspensions as Wigner glasses: dynamical aspects.

Suspensions of charged vesicles in water with added salt are widespread in nature and industrial production. Here we investigate, via Brownian dynamics simulations, a model that grasps the key features of these systems, with bidisperse colloidal beads interacting via a hard-core and an electrostatic double layer potential. Our goal is to focus on a set of interaction parameters that is not generic but measured in recent experiments, and relevant for a class of consumer products, such as liquid fabric softeners. On increasing the volume fraction in a range relevant to real formulation, we show that the dynamics become progressively slower and heterogeneous, displaying the typical signatures of an approaching glass transition. On lowering the salt concentration, which corresponds to increasing the strength and range of the electrostatic repulsion, the emergence of glassy dynamics becomes significantly steeper, and, remarkably, occurs at volume fractions well below the hard-sphere glass transition. The volume fraction dependence of the structural relaxation time at different salt concentration is well described through a functional law inspired by a recently proposed model (Krausser et al 2015 Proc. Natl Acad. Sci. USA 112 13762). According to our results, the investigated system may be thought of as a Wigner glass, i.e. a low-density glassy state stabilized by long-range repulsive interactions. Overall, our study suggests that glassy dynamics plays an important role in controlling the stability of these suspensions.

Flow-induced concentration gradients in shear-banding of branched wormlike micellar solutions.

HYPOTHESIS: Shear-banding of branched wormlike solutions is a topic of active investigation which has not been fully elucidated. Here, we surmise that flow-induced microstructuring in the shear banding regime is associated with spatial concentration gradients. EXPERIMENTS: The experiments focus on the flow-induced behavior of a CTAB/NaSal wormlike micellar system. A unique approach based on a microfluidic-spitter geometry, combined with particle-image velocimetry and high-speed video microscopy, is used to separate the streams flowing out from the core and the near wall zones of the microchannel. FINDINGS: Here, we present the first direct experimental evidence of the correlation between phase separation and shear banding. By increasing the pressure-drop across a microcapillary, the onset of a grainy texture close to the wall, showing a flow-induced demixing effect, is observed. We use a splitter to measure effluent streams from the center and the near-wall zones in terms of viscosity, conductance and dry mass. We observe that phase-separation induced by the flow correlates with chemical concentration gradients. This confirms our hypothesis that shear-induced local de-mixing of the system is strongly related to chemical concentration gradients.

Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with 3 affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYNC2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the 3 affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a truncating change (p.Val141*) in 2 siblings with EvC from a second family, while a newborn with a more severe phenotype carried 2 DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function.

Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non-syndromic microtia and distinctive ear morphology.

Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five-generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non-syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development.

Lipid class dynamics and storage depots in juvenile weakfish Cynoscion regalis and their application to condition assessment.

Lipid class dynamics, the pattern of change in the primary form and location of lipid stores and their relationship with standard length (L(S) ), were investigated in collections of young-of-the-year weakfish Cynoscion regalis for the purpose of determining the utility of this analysis as an indication of condition. The separation of total lipids into individual classes and the analysis of potential storage depots revealed the general patterns of lipid class dynamics and energy storage in C. regalis during their period of juvenile estuarine residency. Phospholipid and cholesterol exhibited moderate but variable (8·1-40·0 and 1·3-21·5 mg g(-1) , respectively) concentrations across the entire juvenile period and were the predominant lipid classes in juveniles <100 mm L(S) , while wax ester concentrations were low (c. 1 mg g(-1) ) and exhibited the least amount of variability among lipid classes. Triacylglycerols (TAG) and free fatty acids (FFA) exhibited similar dynamics, with relatively low concentrations (<15 mg g(-1) ) in individuals ≤100 mm L(S) . In larger juveniles both TAG and FFA concentrations generally increased rapidly, though there was considerable variability in both measures (0·0-199·7 and 0·0-49·7 mg g(-1) , respectively). Increasing levels of lipids, primarily in the form of TAG, with size indicated an accumulation of energy reserves with growth, thus providing an indication of individual condition for larger juveniles. Separate analysis of liver, viscera and the remaining carcass indicated that liver and viscera did not represent a significant depot of TAG reserves. Analysis of samples derived from whole juvenile C. regalis thus provided an accurate estimate of energy reserves.

Is global climate change influencing the overwintering distribution of weakfish Cynoscion regalis?

The pattern of stable isotope signatures in a sub-sample of 67 juvenile weakfish Cynoscion regalis, captured at the mouth of the Christina River, 113 km upstream of the mouth of Delaware Bay (U.S.A) in the autumn of 2000, suggested that they resided at the location since recruitment. The possibility that young C. regalis departed from the generally characteristic life-history pattern of marine migrants at this latitude, i.e. emigrating offshore with the adults in autumn was bolstered by the collection of 69 individuals during the winters of 2000-2006 from the travelling screens of a power plant located at river kilometre 88 including an 118 mm total length juvenile captured in mid-February 2006.

Extrachromosomal genes: a powerful tool in gene targeting approaches.

Several studies, some of which have been updated during the recent workshop entitled Genome Medicine: Gene Therapy for the Millennium (Rome, 30 September-3 October 2001), have highlighted the usefulness of extrachromosomal or episomal genes in gene targeting strategies. Due to the selectable nature of antibiotic resistance and reporter genes, targeted correction of mutated versions of these extrachromosomal genes allows an accurate quantification of correction frequency. In addition, these model systems facilitate and speed up the optimization of critical parameters for the successful application of gene targeting approaches. In fact, type of cell line, gene delivery system, molar ratio of episomal target/therapeutic constructs, nature and design of therapeutic complexes and different recombinative proteins may be critical for the actual feasibility of each method. Although virus-based approaches are now being investigated as well, this article is focusing on the targeted correction of extrachromosomal genes by the use of small DNA fragments (SDF), chimeric RNA/DNA oligonucleotides (RDO) and triplex-forming oligonucleotides (TFO).

Do the four clades of the mtDNA haplogroup L2 evolve at different rates?

Forty-seven mtDNAs collected in the Dominican Republic and belonging to the African-specific haplogroup L2 were studied by high-resolution RFLP and control-region sequence analyses. Four sets of diagnostic markers that subdivide L2 into four clades (L2a-L2d) were identified, and a survey of published African data sets appears to indicate that these clades encompass all L2 mtDNAs and harbor very different geographic/ethnic distributions. One mtDNA from each of the four clades was completely sequenced by means of a new sequencing protocol that minimizes time and expense. The phylogeny of the L2 complete sequences showed that the two mtDNAs from L2b and L2d seem disproportionately derived, compared with those from L2a and L2c. This result is not consistent with a simple model of neutral evolution with a uniform molecular clock. The pattern of nonsynonymous versus synonymous substitutions hints at a role for selection in the evolution of human mtDNA. Regardless of whether selection is shaping the evolution of modern human mtDNAs, the population screening of L2 mtDNAs for the mutations identified by our complete sequence study should allow the identification of marker motifs of younger age with more restricted geographic distributions, thus providing new clues about African prehistory and the origin and relationships of African ethnic groups.

Conservative surgery in breast cancer. Significance of resection margins.

We approached the issue of surgical margins in the conservative treatment of breast cancer by examining the literature germane to four precise questions: At what distance from the macroscopic margin of the tumour should the resection margin be? To what extent do histologically clear resection margins indicate complete local control of the disease? To what extent do histologically involved margins indicate persistence of disease? and Does the local recurrence rate correlate with the status of the resection margin? We propose categorizing margin involvement into five groups (absent, focal, minimal, moderate and extensive involvement) according to strict histological criteria, and assigning increasingly aggressive subsequent treatments according to the extent of any margin involvement.

Tracing European founder lineages in the Near Eastern mtDNA pool.

Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2, 804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.

Variation in the human mitochondrial genome (mtDNA) is now routinely described and used to infer the histories of peoples, by means of one of two procedures, namely, the assaying of RFLPs throughout the genome and the sequencing of parts of the control region (CR). Using 95 samples from the Near East and northwest Caucasus, we present an analysis based on both systems, demonstrate their concordance, and, using additional available information, present the most refined phylogeny to date of west Eurasian mtDNA. We describe and apply a nomenclature for mtDNA clusters. Hypervariable nucleotides are identified, and the relative mutation rates of the two systems are evaluated. We point out where ambiguities remain. The identification of signature mutations for each cluster leads us to apply a hierarchical scheme for determining the cluster composition of a sample of Berber speakers, previously analyzed only for CR variation. We show that the main indigenous North African cluster is a sister group to the most ancient cluster of European mtDNAs, from which it diverged approximately 50,000 years ago.

[Diagnosis and treatment of traumatic diaphragmatic hernia with delayed presentation]. / Diagnosi e trattamento dell'ernia traumatica del diaframma a tardiva presentazione.

AIM: To evaluate the clinical picture, diagnostic techniques and most appropriate treatment in traumatic diaphragmatic hernia with delayed presentation on the basis of personal experience and in the light of other published studies. EXPERIMENTAL DESIGN: Review of cases treated. SETTING: Patients treated in University General Surgery wards. PATIENTS: Those patients in whom diagnosis was made some time after trauma and after the acute event were selected from a group of patients with traumatic diaphragmatic hernia. SURGERY: All patients underwent surgery to reduce hernia and repair the diaphragmatic lesion. MEASUREMENTS: All clinical findings were examined together with the tests performed and the type of treatment carried out. RESULTS: The diagnosis was made between 3 months and 3 years after the injury. Three patients presented manifest symptoms of high intestinal occlusion on entry. Radiological alterations were present in standard chest X-rays in all patients and digestive tract contrast radiography was positive for the diagnosis of hernia in 3 out of 4 cases in which it was performed; a preoperative diagnosis of hernia was obtained in 4 cases. Patients were operated using a thoracotomy (3 cases) or combined laparothoracotomy access (2 cases); the diaphragmatic lesion, localised in all cases in the cupula of the left hemidiaphragm, was repaired using separate sutures in non-reabsorbable material without the use of grafts. One patient died postoperatively owing to septic complications. CONCLUSIONS: traumatic diaphragmatic hernia with delayed presentation involves severe complications that increase morbidity and operating mortality.

[Primary germinal tumors of the mediastinum: our experience in 9 cases]. / I tumori germinali primitivi del mediastino: nostra esperienza in nove casi.

9 patients (8 males 1 female, middle age 24.3 years, range 20-41) affected by primary mediastinal germ cell tumor were surgically treated in our department. They were 4 seminomas, 2 embryonal carcinomas, 1 malignant teratoma and 2 benign teratomas. Three patients were asymptomatic; cough, dyspnea and chest pain were the most frequently observed symptoms. The staging work-up did not show signs of metastatic disease in the malignant types. Benign teratomas underwent complete excision. In one patient suffering from seminoma radiotherapy and chemotherapy caused complete remission of the disease. In the others cases remission of the neoplasm was obtained by resection and adjuvant therapy in 3 cases, by neoadjuvant treatment and excision of the residual mass in 3 cases. Among the patients suffering from seminoma, 2 are dead at 60 months since initial treatment and 2 are alive at 132 and 120 months respectively. Among the patients with malignant nonseminomatous tumours, 2 are alive at 60 and 36 months and 1 patient is dead at 13 months. Two patients with benign teratoma are alive at 189 and 168 months respectively. At present a multimodality treatment including surgery, radiotherapy and cisplatin-based combination chemotherapy, give the most satisfactory results in the treatment of malignant mediastinal germ cell tumours.

[What significance should be attributed to the high rate of erythrocyte sedimentation in elderly subjects?]. / Quale valore attribuire all'alta velocità di eritrosedimentazione nei soggetti anziani?

The usefulness of the erythrocyte sedimentation rate as a diagnostic tool is asserted, not only for checking disease progress but also because an increase of more than 20 mm is an indication that the patient should be further examined for diseases which are not yet clinically evident.

Sobre o uso de bacilos esporulados aerobios, por via oral, no tratamento de diarreias infecciosas. Acao sobre Salmonellas, Shigellas, Proteus e E.Coli patogenicos. / On the use of sporulated aerobic bacilli by oral administration, in the treatment of infectious diarrheas. Effect on Salmonellas, Shigellas, Proteus and E. Coli pathogenic

Os bacilos esporulados aerobicos constituem uma arma bastante eficiente no combate as diarreias infecciosas provocadas pela E. coli patogenica, Shigellas, Salmonellas, Proteus, Pseudomonas e Staphilococcus. Suas enzimas (proteases, amilases e lipase) reconstituem os processos digestivos e normalizam as evacuacoes. O tratamento de 3.500 pacientes mostraram a grande importancia desses microorganismos nas diarreias infecciosas, atendendo todos os angulos da materia, agente infeccioso, processo digestivo enzimatico, vitaminas e flora