A review of thermal impact of surface acoustic waves on microlitre droplets in medical applications

The surface acoustic waves (SAW) propagate inside the microdroplets resulting in kinetic and thermal impacts. The kinetic drives fluid particles inside the droplet while thermal impact increases the liquid’s temperature. This paper provides a comprehensive review of the research investigations related to internal kinetics and heating inside the microdroplet caused by the acoustic waves. The main factors that affect the kinetics and convection heat transfer are the piezoelectric materials, shape of the interdigital transducer (IDT) and mode of acoustic waves. Internal streaming (kinetic) leads to particle mixing, particle manipulation, cell sorting, cell patterning, cell separation, measuring the concentration of immunoglobulin and so forth. The effect of changing the mode of waves and the shape of IDT on the relevant applications are presented. Internal convection heat transfer is important where heating of the liquid is essential for many applications such as monitoring blood coagulation in the human plasma and an acoustic tweezer for particle trapping. Experimental methods developed by researchers to realise uniform temperature with constant heating and cooling cycles are also discussed. Such methods are widely used in the polymerase chain reaction (PCR) to detect COVID-19 infection. The heating of the droplet can be efficiently controlled by changing the input power and by varying the duty factor

Regulatory de novo mutations underlying intellectual disability

The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID

Mortality from external causes in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System Sites.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology

CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer

Background: Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. Main text: Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of “one-size-fits-all” therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. Conclusion: With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine

Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work

Factors underlying age-related changes in discrete aiming

Age has a clear impact on one’s ability to make accurate goal-directed aiming movements. Older adults seem to plan slower and shorter-ranged initial pulses towards the target, and rely more on sensory feedback to ensure endpoint accuracy. Despite the fact that these age-related changes in manual aiming have been observed consistently, the underlying mechanism remains speculative. In an attempt to isolate four commonly suggested underlying factors, young and older adults were instructed to make discrete aiming movements under varying speed and accuracy constraints. Results showed that older adults were physically able to produce fast primary submovements and that they demonstrated similar movement-programming capacities as young adults. On the other hand, considerable evidence was found supporting a decreased visual feedback-processing efficiency and the implementation of a play-it-safe strategy in older age. In conclusion, a combination of the latter two factors seems to underlie the age-related changes in manual aiming behaviour

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

<p>Abstract</p> <p>Background</p> <p>Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities.</p> <p>Methods</p> <p>We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected.</p> <p>Results</p> <p>Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics.</p> <p>Conclusions</p> <p>The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.</p