Multivariate Data Analysis Methodology to Solve Data Challenges Related to Scale‐Up Model Validation and Missing Data on a Micro‐Bioreactor System

Multivariate data analysis (MVDA) is a highly valuable and significantly underutilized resource in biomanufacturing. It offers the opportunity to enhance understanding and leverage useful information from complex high‐dimensional data sets, recorded throughout all stages of therapeutic drug manufacture. To help standardize the application and promote this resource within the biopharmaceutical industry, this paper outlines a novel MVDA methodology describing the necessary steps for efficient and effective data analysis. The MVDA methodology is followed to solve two case studies: a “small data” and a “big data” challenge. In the “small data” example, a large‐scale data set is compared to data from a scale‐down model. This methodology enables a new quantitative metric for equivalence to be established by combining a two one‐sided test with principal component analysis. In the “big data” example, this methodology enables accurate predictions of critical missing data essential to a cloning study performed in the ambr15 system. These predictions are generated by exploiting the underlying relationship between the off‐line missing values and the on‐line measurements through the generation of a partial least squares model. In summary, the proposed MVDA methodology highlights the importance of data pre‐processing, restructuring, and visualization during data analytics to solve complex biopharmaceutical challenges.     

Homing in the Mangrove Swimming Crab Thalamita crenata (Decapoda: Portunidae)

On the Kenyan coast, Thalamita crenata confines itself to a defined system of crevices and forages, swimming in a few cm of water, within a radius of about 5 m from its shelter. A field study was designed to analyse this crab's ability to find its shelter after being moved away from it. Crabs were displaced, being kept under water, with full vision of the sky and landscape and released 5 m away from their refuges, at a maximum depth of 50 cm. They were able to return to their shelters within 1 h and followed initial directions which were well orientated towards home. T. crenata was still well orientated and successful in returning home during nocturnal displacements and even after trials in which the landscape was altered. Only blind crabs were neither initially orientated towards home nor successful in returning within two tidal cycles of their release. The hypothesis that this swimming crab could use orientating information obtained during the outward displacement was then tested. Specimens were dislocated following a non-linear outward path, without vision of the surrounding landscape; other crabs were carried to a false release point and then carried in a closed container to the actual release point. Finally, three kinds of detour experiments were performed. In all these trials the directions chosen by the crabs were still clustered around the home direction and homing success was again high. These results exclude homing mechanisms based on random search strategies or on egocentric mechanisms, such as path integration. The most probable hypothesis is that T. crenata organizes some visual cues in a map-like arrangement and, detecting these cues from any release point within its home range, uses this map to return home.     

Qualitative distinction of congeneric and introgressive mangrove species in mixed patchy forest assemblages using high spatial resolution remotely sensed imagery (IKONOS)

This paper is a preliminary report of the ability of IKONOS multispectral satellite imagery with a very high spatial resolution of 1 metre to distinguish two mangrove species in Sri Lanka belonging to the same genus (Rhizophora apiculata and R. mucronata). Not only is this an advancement for the monitoring of forests, it is even more important considering their patchy nature in Sri Lankan mangroves (in contrast to classically zoned forests). Apart from congeneric distinction, intro‐gressive species (Acrostichum aureum) can also be detected from IKONOS imagery, which is important in the early warning for cryptic ecological changes that may affect mangrove species composition (both floral and faunal) and functioning. The results tabulate the usage of various image composites, transformations and classifications, and indicate the danger of too much detail in remote sensing, and the need to apply an optimum resolution. We also highlight that the highest resolutions (as in pansharpened multispectral composites) remain invaluable for visual ecological investigations, which are not at all outdated by new digital satellite images of (sub)metre spatial resolution and their possibility for computer‐aided analysis.     

Cross-cultural variation in men's preference for sexual dimorphism in women's faces

Both attractiveness judgements and mate preferences vary considerably cross-culturally. We investigated whether men''s preference for femininity in women''s faces varies between 28 countries with diverse health conditions by analysing responses of 1972 heterosexual participants. Although men in all countries preferred feminized over masculinized female faces, we found substantial differences between countries in the magnitude of men''s preferences. Using an average femininity preference for each country, we found men''s facial femininity preferences correlated positively with the health of the nation, which explained 50.4% of the variation among countries. The weakest preferences for femininity were found in Nepal and strongest in Japan. As high femininity in women is associated with lower success in competition for resources and lower dominance, it is possible that in harsher environments, men prefer cues to resource holding potential over high fecundity.     

Zn2+-Aβ40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons

The roles of metal ions in promoting amyloid β-protein (Aβ) oligomerization associated with Alzheimer disease are increasingly recognized. However, the detailed structures dictating toxicity remain elusive for Aβ oligomers stabilized by metal ions. Here, we show that small Zn(2+)-bound Aβ1-40 (Zn(2+)-Aβ40) oligomers formed in cell culture medium exhibit quasi-spherical structures similar to native amylospheroids isolated recently from Alzheimer disease patients. These quasi-spherical Zn(2+)-Aβ40 oligomers irreversibly inhibit spontaneous neuronal activity and cause massive cell death in primary hippocampal neurons. Spectroscopic and x-ray diffraction structural analyses indicate that despite their non-fibrillar morphology, the metastable Zn(2+)-Aβ40 oligomers are rich in β-sheet and cross-β structures. Thus, Zn(2+) promotes Aβ40 neurotoxicity by structural organization mechanisms mediated by coordination chemistry.     

Sleep and psychological factors are associated with meeting discharge criteria to return to sport following ACL reconstruction in athletes

This study aimed to determine if sleep quality and psychological factors were associated with time to meet the discharge criteria to return to sport (RTS) following anterior cruciate ligament reconstruction (ACL-R) among athletes. A cohort-study design included 89 athletes following ACL-R. Each participant completed a battery of questionnaires at 6 different time points: within 3 days of injury occurrence and at post-surgery (1.5 m, 3 m, 4.5 m, 6 m and when discharge criteria were met). Assessment included sleep quality and quantity, symptoms of depression, anxiety, stress, psychological readiness to RTS and fear of re-injury. The primary outcome was the time needed to meet all discharge criteria to RTS. Sleep parameters and psychological factors were not associated with time to meet the discharge criteria to RTS. However, athletes that had lower scores of anxiety (OR 1.2 (95% CI 1.0, 1.3) and insomnia (OR 1.2 (95% CI 1.0, 1.3) at baseline were more likely to meet the RTS discharge criteria. Athletes with better sleep quality at 3m, 4.5m and 6m were more likely to meet the RTS discharge criteria OR 1.3 (95% CI 1.1, 1.7), 2.0 (95% CI 1.1–3.4) and 1.4 (95% CI 1.0, 1.9) respectively. Sleep quality and psychological factors were not associated with time to meet the discharge criteria to RTS but impacted whether athletes adhered and completed their rehabilitation program or not. Monitoring sleep quality and psychological factors of athletes before and following ACL-R surgery is important to identify athletes who could have difficulties in adhering to and completing their rehabilitation program to RTS.     

Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3

Translationally Controlled Tumour Protein (TCTP), a highly conserved protein present in all eukaryotic organisms, has a number of intracellular and extracellular functions including an anti-apoptotic role. TCTP was recently shown to interact with both p53 and HDM2, inhibiting auto-ubiquitination of the latter and thereby promoting p53 degradation. In this study, we further investigated the interaction between TCTP and HDM2, mapping the reciprocal binding sites of TCTP and HDM2. TCTP primarily interacts with the N-terminal, p53-binding region of HDM2 through its highly basic domain 2. Furthermore, we discovered that Nutlin-3, a small molecule known to promote apoptosis and cell cycle arrest by blocking binding between HDM2 and p53, has a similar inhibitory effect on the interaction of HDM2 and TCTP. This result may provide an additional explanation of how Nutlin-derived compounds currently in clinical trials function to promote apoptosis in cancer cells.     

Health related quality of life in patients with type 2 diabetes mellitus in iran: a national survey

Introduction

The aim of this study was to measure health-related quality of life (HRQoL) in Iranian people with Type 2 Diabetes Mellitus using two different measures and examines which socio-demographic and diabetes-related characteristics are associated with better quality of life based on a nationally distributed sample.

Methods

A multi-stage cluster sampling method was used to select 3472 subjects as a part of Iranian surveillance of risk factors of non-communicable disease (ISRFNCD). EuroQol-5 Dimensions questionnaire (EQ-5D) and Visual Analog Scale (VAS) were employed to measure HRQoL. Binary logistic and Tobit regression models were used to investigate factors associated with EQ-5D results.

Results

The mean age of subjects was 59.4 years (SD = 11.7), 61.3% were female and had 8.08 years (SD = 6.7) known duration of diabetes. The patients reported “some or extreme problems” most frequently in Pain/Discomfort (69.3%) and Anxiety/Depression (56.6%) dimensions of EQ-5D. The mean EQ-5D and VAS score were 0.70 (95% CI 0.69–0.71) and 56.8 (95% CI 56.15–57.5) respectively. Female gender, lower education, unemployment, long duration of diabetes, diabetes-related hospitalization in past years and having nephropathy and lower extremity lesions were associated with higher probabilities of reporting “some or extreme problems” in most dimensions of EQ-5D in binary logistic regression models. The same factors in addition to retinopathy were significantly associated with lower levels of HRQoL in Tobit regression analysis too.

Conclusions

The study findings indicate that patients with diabetes in Iran suffer from relatively poor HRQoL. Therefore much more attention should be paid to main determinants of HRQoL to identify and implement appropriate policies for achieving better management of diabetes and ultimately improving the quality of life of diabetic patients in this region.     

Mental Disorders in Megacities: Findings from the S?o Paulo Megacity Mental Health Survey,Brazil

Background

World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. São Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders.

Methods and Results

A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year.

Discussion

Adults living in São Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.