Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the single nucleotide polymorphism 309 (SNP309, T -> G) in the promoter region of the MDM2 gene is important for tumor development; however, with regards to breast cancer, inconsistent associations have been reported worldwide. It is speculated that these conflicting results may have arisen due to different patient subgroups and ethnicities studied. For the first time, this study explores the effect of the MDM2 SNP309 genotype on Taiwanese breast cancer patients.</p> <p>Methods</p> <p>Genomic DNA was obtained from the whole blood of 124 breast cancer patients and 97 cancer-free healthy women living in Taiwan. MDM2 SNP309 genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. The multivariate logistic regression and the Kaplan-Meier method were used for analyzing the risk association and significance of age at diagnosis among different MDM2 SNP309 genotypes, respectively.</p> <p>Results</p> <p>Compared to the TT genotype, an increased risk association with breast cancer was apparent for the GG genotype (OR = 3.05, 95% CI = 1.04 to 8.95), and for the TG genotype (OR = 2.12, 95% CI = 0.90 to 5.00) after adjusting for age, cardiovascular disease/diabetes, oral contraceptive usage, and body mass index, which exhibits significant difference between cases and controls. Furthermore, the average ages at diagnosis for breast cancer patients were 53.6, 52 and 47 years for those harboring TT, TG and GG genotypes, respectively. A significant difference in median age of onset for breast cancer between GG and TT+TG genotypes was obtained by the log-rank test (p = 0.0067).</p> <p>Conclusion</p> <p>Findings based on the current sample size suggest that the MDM2 SNP309 GG genotype may be associated with both the risk of breast cancer and an earlier age of onset in Taiwanese women.</p

Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study

10.1186/1471-2334-11-123BMC Infectious Diseases11-BIDM

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

OBJECTIVES: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. METHODS: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. RESULTS: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs$3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). CONCLUSIONS: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs

Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

OBJECTIVES: Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. METHODS: Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. RESULTS: In this study, each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. CONCLUSION: These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients

A development of assistant surgical robot system based on surgical-operation-by-wire and hands-on-throttle-and-stick

BACKGROUND: Robot-assisted laparoscopic surgery offers several advantages compared with open surgery and conventional minimally invasive surgery. However, one issue that needs to be resolved is a collision between the robot arm and the assistant instrument. This is mostly caused by miscommunication between the surgeon and the assistant. To resolve this limitation, an assistant surgical robot system that can be simultaneously manipulated via a wireless controller is proposed to allow the surgeon to control the assistant instrument. METHODS: The system comprises two novel master interfaces (NMIs), a surgical instrument with a gripper actuated by a micromotor, and 6-axis robot arm. Two NMIs are attached to master tool manipulators of da Vinci research kit (dVRK) to control the proposed system simultaneously with patient side manipulators of dVRK. The developments of the surgical instrument and NMI are based on surgical-operation-by-wire concept and hands-on-throttle-and-stick concept from the earlier research, respectively. Tests for checking the accuracy, latency, and power consumption of the NMI are performed. The gripping force, reaction time, and durability are assessed to validate the surgical instrument. The workspace is calculated for estimating the clinical applicability. A simple peg task using the fundamentals of laparoscopic surgery board and an in vitro test are executed with three novice volunteers. RESULTS: The NMI was operated for 185 min and reflected the surgeon’s decision successfully with a mean latency of 132 ms. The gripping force of the surgical instrument was comparable to that of conventional systems and was consistent even after 1000 times of gripping motion. The reaction time was 0.4 s. The workspace was calculated to be 8397.4 cm(3). Recruited volunteers were able to execute the simple peg task within the cut-off time and successfully performed the in vitro test without any collision. CONCLUSIONS: Various experiments were conducted and it is verified that the proposed assistant surgical robot system enables collision-free and simultaneous operation of the dVRK’s robot arm and the proposed assistant robot arm. The workspace is appropriate for the performance of various kinds of surgeries. Therefore, the proposed system is expected to provide higher safety and effectiveness for the current surgical robot system

Fault Detection and Isolation of Nonlinear Systems: An Unknown Input Observer Approach With Sum-of-Squares Techniques

[[abstract]]This paper presents a novel nonlinear unknown input observer (UIO) design method for fault detection and isolation (FDI) of a class of nonlinear affine systems. By using sum-of-squares (SOS) theory and Lie geometry as the main tools, we demonstrate how to relax the rank constraint in the traditional UIO approach and simplify the design procedure, especially for the polynomial nonlinear systems. Meanwhile, we show that the detection and isolation thresholds based on the L-2 gains can be easily obtained via optimization formulated in terms of SOS. Simulation examples are given to illustrate the design procedure and the advantages. [DOI: 10.1115/1.4006074][[note]]SC

Consensus of multi-agent systems with general linear dynamics via dynamic output feedback control

[[abstract]]This study addresses consensus problems of multi-agent systems (MASs) using dynamic output feedback control under both fixed and switching topologies. We aim to exploit the information structure for the consensusability of MASs. Necessary and sufficient conditions are presented in terms of detectability and stabilisability of the agents, graph topology, and some matrix inequality constraints. These conditions explicitly reveal how consensusability is affected by the intrinsic dynamics of the agents, the communication topology and available information. In addition, this paper provides several constructive procedures for protocol design to achieve consensus, and establishes the so-called separation principle, which simplifies the design procedure greatly.[[note]]SC

Proportional Navigation With Delayed Line-of-Sight Rate

[[abstract]]This brief discusses the convergence analysis of proportional navigation (PN) guidance law in the presence of delayed line-of-sight (LOS) rate information. The delay in the LOS rate is introduced by the missile guidance system that uses a low cost sensor to obtain LOS rate information by image processing techniques. A Lyapunov-like function is used to analyze the convergence of the delay differential equation (DDE) governing the evolution of the LOS rate. The time-to-go until which decreasing behaviour of the Lyapunov-like function can be guaranteed is obtained. Conditions on the delay for finite time convergence of the LOS rate are presented for the linearized engagement equation. It is observed that in the presence of line-of-sight rate delay, increasing the effective navigation constant of the PN guidance law deteriorates its performance. Numerical simulations are presented to validate the results.[[note]]SC