Measuring Inaccessible Residual Stresses Using Multiple Methods and Superposition

The traditional contour method maps a single component of residual stress by cutting a body carefully in two and measuring the contour of the cut surface. The cut also exposes previously inaccessible regions of the body to residual stress measurement using a variety of other techniques, but the stresses have been changed by the relaxation after cutting. In this paper, it is shown that superposition of stresses measured post-cutting with results from the contour method analysis can determine the original (pre-cut) residual stresses. The general superposition theory using Bueckner’s principle is developed and limitations are discussed. The procedure is experimentally demonstrated by determining the triaxial residual stress state on a cross section plane. The 2024- T351 aluminum alloy test specimen was a disk plastically indented to produce multiaxial residual stresses. After cutting the disk in half, the stresses on the cut surface of one half were determined with X-ray diffraction and with hole drilling on the other half. To determine the original residual stresses, the measured surface stresses were superimposed with the change stress calculated by the contour method. Within uncertainty, the results agreed with neutron diffraction measurements taken on an uncut disk

Self-Organization of Anastral Spindles by Synergy of Dynamic Instability, Autocatalytic Microtubule Production, and a Spatial Signaling Gradient

Assembly of the mitotic spindle is a classic example of macromolecular self-organization. During spindle assembly, microtubules (MTs) accumulate around chromatin. In centrosomal spindles, centrosomes at the spindle poles are the dominating source of MT production. However, many systems assemble anastral spindles, i.e., spindles without centrosomes at the poles. How anastral spindles produce and maintain a high concentration of MTs in the absence of centrosome-catalyzed MT production is unknown. With a combined biochemistry-computer simulation approach, we show that the concerted activity of three components can efficiently concentrate microtubules (MTs) at chromatin: (1) an external stimulus in form of a RanGTP gradient centered on chromatin, (2) a feed-back loop where MTs induce production of new MTs, and (3) continuous re-organization of MT structures by dynamic instability. The mechanism proposed here can generate and maintain a dissipative MT super-structure within a RanGTP gradient

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.

Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression

The courage to change: Patient perceptions of 12-Step fellowships

<p>Abstract</p> <p>Background</p> <p>From a health services perspective, peer-based resources merit special attention. Participation in self-help fellowships, like the Twelve Step Groups (TSGs), have been shown to improve outcomes of patients with substance use disorder (SUD) and they represent a valuable adjunct to the SUD treatment system. This study investigated the relationship between patient perceptions of TSGs and the intent to participate in TSGs after receiving detoxification treatment.</p> <p>Methods</p> <p>We included 139 patients that entered a detoxification unit (detox) in Kristiansand, Norway. We analyzed factors associated with the intention to participate in TSGs post-discharge with contingency tables and ordinal regression analysis.</p> <p>Results</p> <p>Forty-eight percent of patients had participated in TSGs before entering detox. Respondents saw more advantages than disadvantages in TSG participation, but only 40% of patients showed high intentions of participating in TSGs post-discharge. A high intention to participate in TSGs was most strongly correlated with the notion that participation in TSGs could instill the courage to change. In a multivariate analysis, the perception that TSGs were beneficial was the strongest factor related to a high intention of TSG participation after treatment.</p> <p>Conclusions</p> <p>Our findings increased the understanding of factors most likely to influence decisions to attend TSGs in SUD treatment contexts with uncommon TSG participation. Our results suggested that the majority of patients may be sufficiently influenced by highlighting the potential gains of TSG participation. Treatment programs that do not focus on self-help group attendance during and after treatment should consider implementing facilitative measures to enhance utilization of these fellowships.</p

Persistence of Mycoplasma genitalium Following Azithromycin Therapy

BACKGROUND: To determine clinical outcomes and cure rates for M.genitalium genital infection in men and women following azithromycin 1 g. METHODOLOGY: Patients attending Melbourne Sexual Health Centre between March 2005 and November 2007 with urethritis/epididymitis, cervicitis/pelvic inflammatory disease and sexual contacts of M.genitalium were tested for M.genitalium by polymerase chain reaction (PCR). M.genitalium-infection was treated with 1 g of azithromycin and a test-of-cure (toc) was performed one month post-azithromycin. Response to azithromycin, and response to moxifloxacin (400 mg daily for 10 days) in individuals with persistent infection post-azithromycin, was determined. PRINCIPAL FINDINGS: Of 1538 males and 313 females tested, 161 males (11%) and 30 females (10%) were infected with M.genitalium. A toc was available on 131 (69%) infected individuals (median = 36 days [range 12-373]). Of 120 individuals prescribed azithromycin only pre-toc, M.genitalium was eradicated in 101 (84%, 95% confidence intervals [CI]: 77-90%) and persisted in 19 (16%, 95% CI: 10-23%). Eleven individuals with persistent infection (9%, 95% CI: 5-15%) had no risk of reinfection from untreated-partners, while eight (7%, 95% CI: 3-12%) may have been at risk of reinfection from doxycycline-treated or untreated-partners. Moxifloxacin was effective in eradicating persistent infection in all cases not responding to azithromycin. Patients with persistent-M.genitalium were more likely to experience persistent symptoms (91%), compared to patients in whom M.genitalium was eradicated (17%), p<0.0001. CONCLUSION: Use of azithromycin 1 g in M.genitalium-infected patients was associated with unacceptable rates of persistent infection, which was eradicated with moxifloxacin. These findings highlight the importance of follow-up in M.genitalium-infected patients prescribed azithromycin, and the need to monitor for the development of resistance. Research to determine optimal first and second-line therapeutic agents for M.genitalium is needed

Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly

Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition

Attitudes towards 12-step groups and referral practices in a 12-step naive treatment culture; a survey of addiction professionals in Norway

<p>Abstract</p> <p>Background</p> <p>Addressing substance use disorders effectively requires a long-term approach. Substance abuse treatment is typically of short duration; referring patients to Twelve Step based self-help groups (TSGs) – e.g. Narcotics Anonymous, represents a promising complementary recovery resource. Clinicians' attitudes and referral practices towards the TSGs have mainly been studied in countries with high integration of the 12-step philosophy in their substance abuse services and where the TSGs are widely available, such as the US. In Norway, there are currently 294 weekly TSG meetings (6 per 100,000 inhabitants). This study describes clinicians' attitudes and referral practices to TSGs in Norway where health authorities seek to promote self-help participation, but where the treatment culture is unfamiliar with 12-step fellowships.</p> <p>Methods</p> <p>Data collected by a self-administered questionnaire, adapted from established US and UK instruments. Information covered the attitudes, knowledge and referral practices towards TSGs among addiction treatment professionals in Norway in mid 2008.</p> <p>Results</p> <p>The return rate was 79.7% (n = 291). Participants had moderately positive attitude scores towards TSGs, but referral to these groups among Norwegian addiction professionals was low, as was the level of knowledge about TSGs. More than six out of ten did not refer any patients to TSGs in the previous week. Local variation with more referrals to TSGs in the county with the one established 12-step treatment facility was observed. Respondents' integration of the 12-steps in their own treatment work, higher self-efficacy for making a successful referral, and greater TSG knowledge were associated with referring patients.</p> <p>Conclusion</p> <p>Low referral rates to TSGs point to the need for education and training to raise the awareness and knowledge about it among addiction professionals unfamiliar with these 12-step fellowships. Training should focus on the usefulness of these groups for all types of treatment models regardless of therapeutic orientation. Increased knowledge is expected to lead to higher referral rates, which in turn would maximize the likelihood of positive long-term patient outcomes.</p