Man Up: Integrating Fatherhood and Community Engagement

In recent years, there has been an increase in programs designed to promote involved and responsible fatherhood. While the literature provides insight into how existing organizations serving fathers can improve the quality of their service delivery, little is known about starting a fatherhood program from the ground up. This article contributes to the needed discussion on such programs by exploring the development of the Man Up fatherhood program. Featured in this discussion is Man Up’s program development model, which combines parent education and community engagement events and activities and engages fathers at a level that transcends their involvement as program participants or research subjects. Engaging and promoting responsible fatherhood through community events is one of the ways that distinguishes Man Up from other fatherhood programs

Vector-free microfluidic platform for intracellular delivery of macromolecules

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013."June 2016." Cataloged from PDF version of thesis.Includes bibliographical references (p. 158-165).Intracellular delivery of material is a long-standing challenge for both therapeutic and research applications. Existing technologies rely on a variety of mechanisms to facilitate delivery. Vector-based methods, such as polymeric nanoparticles and liposomes, form complexes with the target material and subsequently facilitate its uptake by the cell of interest, often through endocytosis. Although effective in some applications, these methods have had difficulty translating to patient-derived primary cells, especially stem cells and immune cells. Moreover, these vectors are often limited in the range of target materials they can deliver and leave much material trapped in endocytotic vesicles. Physical methods, such as electroporation and sonoporation, have been able to address some of the challenges with vector-based methods by providing a platform for physical disruption of the cell membrane. By eliminating the need for vector materials and circumventing the endocytotic pathway, these methods have shown an advantage in some applications, especially those involving primary cells that are recalcitrant to vector-based methods. However, both electroporation and sonoporation suffer from high cell toxicity and have had limited success in delivering materials such as proteins and nanomaterials. Electroporation in particular has been shown to damage certain target materials, such as quantum dots. Microinjection, an alternative method in which cells are punctured by a microneedle, can address a variety of target materials and cell types however its low throughput has hindered its adoption for most applications. There is thus a need for more effective intracellular delivery methods. This dissertation describes a microfluidic approach to intracellular delivery that seeks to embody the advantages of a physical method, while mitigating issues related to toxicity and damage to the target material. In our method, the cells of interest are prepared in suspension with the target delivery material and flown through a parallel network of microfluidic channels. Each channel contains a constriction point where the cells are rapidly deformed, or squeezed, as they pass through. This process induces temporary disruption of the cell membrane thereby enabling diffusive transport of material from the surrounding buffer into the cell cytosol. These disruptions persist for less than 5min before membrane integrity is fully restored. This method has thus far been demonstrated in over 15 cell types and has been able to deliver a variety of functional materials including, DNA, RNA, proteins, quantum dots, carbon nanotubes, and small molecules. Our cell squeezing technology has further illustrated its enabling potential in a number of applications detailed herein. Quantum dots are a promising alternative to organic fluorescent dyes due to their superior spectral properties and stability. These nanoparticles have much potential as imaging agents in vitro and in vivo. Delivery of undamaged quantum dots to the cell cytoplasm has been a challenge with existing techniques. Vector-based methods have resulted in aggregation and endosomal sequestration of quantum dots while electroporation can damage the semi-conducting particles and aggregate delivered dots in the cytosol. In our work, we demonstrated efficient cytosolic delivery of quantum dots without inducing aggregation, trapping material in endosomes, or significant loss of cell viability. Moreover, we have shown that individual quantum dots delivered by this approach are detectable in the cell cytosol, thus illustrating the potential of this technique for single molecule tracking studies. These results indicate that our method could potentially be implemented as a robust platform for quantum dot based imaging in a variety of applications. The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has much potential in its ability to address existing challenges in regenerative medicine by providing a patient-specific source of pluripotent stem cells to generate new tissue. The mechanism of this reprogramming process, however, is still poorly understood and existing technologies suffer from chronically low reprogramming efficiencies (<4%). Moreover, many existing approaches to reprogramming rely on viral vectors to facilitate the delivery of the target transcription factors - these vectors are considered inappropriate for clinical applications due to safety concerns. Cytosolic delivery of protein transcription factors is a possible alternative to viral and plasmidbased reprogramming techniques. Direct protein delivery would negate the current safety concerns with viral and plasmid-based methods as it could not cause potentially tumorigenic changes in the genome. In our work, we implemented the cell squeezing technology as a method to deliver protein transcription factors to the cytosol of primary human fibroblasts. These studies yielded colonies of pluripotent stem cells that appeared to be fully functional. Moreover, the efficiency of this procedure was 10-100x higher than the current state-of-the-art protein reprogramming methods. The versatility of our delivery technology thus provides a promising platform for further study of the reprogramming process and the development of more efficient, clinically applicable, reprogramming procedures. Finally, the technology described herein has been implemented in cancer vaccine applications. Some recent immunotherapies against cancer have focused on the use of dendritic cells as antigen presenting cells. These cells are capable of presenting cancer antigens to other immune cell subsets and prompting a powerful immune response against the target cell type. A significant challenge for these therapies, however, is that current methods to induce antigen presentation in dendritic cells are often inefficient and can potentially induce a parallel regulatory response that reduces treatment efficacy. In our work, we have implemented the device as a platform for direct cytosolic delivery of the target antigen to dendritic cells. This approach could enable effective presentation of the target antigen while minimizing the development of a regulatory response. Our results indicate that this approach can produce effective antigen presentation in vitro, as measured by CD8 T cell coculture assays. Moreover, we have demonstrated effective antigen presentation in B cells, a more desirable clinical alternative to dendritic cells. These results thus illustrate the potential of this technology to be implemented as an enabling, patient-specific vaccination platform with minimal side-effects. In summary, we have developed a robust, high-throughput approach to intracellular delivery. In the described technique, cytosolic delivery is facilitated by the temporary disruption of the cell membrane in response to rapid mechanical deformation of the cell in a microfluidic channel. This technology seeks to addresses some of the challenges of existing vector-based and physical poration methods, such as endocytosis, translation to primary cells, and cell toxicity. Our results in quantum dot, cell reprogramming, and cancer vaccine applications illustrate the strengths of this system. Although in its infancy, this technology has demonstrated the potential to enable a range of clinical and research applications. In the future, better understanding of the underlying mechanism and improvements to the system could produce substantial gains in performance and allow this technique to be widely adopted by researchers and clinicians.by Armon R. Sharei.Ph.D

Democracy in a de-civilizing age: The rise of shameless personal truths

In this paper, we articulate an argument that suggests we need to look to broad, yet often quite subtle, societal and cultural changes, in order to better understand post-truth politics. We argue that democracy, ontologically premised on the atomized individual as the legitimate social agent, (Hay 2007) is itself being destabilised. This disruption is due in part to a shift in our conception of 'self' that is both corroding the core pillars of our civilising process and altering the nature of our engagement with democratic politics. The historic processes of a civilising culture are outlined in order to argue that the power of our neoliberal consumer culture has generated a ‘decivilising turn’, characterized by the rise of shame thresholds and narcissistic personalities. We then illustrate how these cultural changes produce a climate welcoming of ‘Post-truth’, linking this most specifically to the contemporary political landscape. Civic life resides most acutely in the customs and conventions upheld through the practice of our public dealings with others. The more entrenched, the less easily it can be disrupted by maverick acts and demagogues’ deeds. However, when those in positions of high office show little self-restraint, and sufficient numbers of the populous don't care, the norms democracy depends on are vulnerable to 'charlatan' leaders and populist causes. Here, we offer a picture of democracy in a ‘decivilising’ age where shameless personal truth is privileged. Please note that the start of the introduction contains words that some readers may find offensive

Understanding student evaluations : a black faculty perspective.

Student evaluations of faculty teaching are critical components to the evaluation of faculty performance. These evaluations are used to determine teaching effectiveness and they influence tenure and promotion decisions. Although they are designed as objective assessments of teaching performance, extraneous factors, including the instructors’ race, can affect the composition and educational atmosphere at colleges and universities. In this reflection, we briefly review some literature on the use and utility of student evaluations and present narratives from social work faculty in which students’ evaluation contained perceived racial bias

Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?—observations from the UK JSLE Cohort Study

Objectives: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. / Methods: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. / Results: At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). / Conclusion: In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes

A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors

INTRODUCTION: PARP-1 (polyADP-ribose polymerase-1) is known to be activated in response to DNA damage, and activated PARP-1 promotes DNA repair. However, a recently disclosed alternative mechanism of PARP-1 activation by phosphorylated externally regulated kinase (ERK) implicates PARP-1 in a vast number of signal-transduction networks in the cell. Here, PARP-1 activation was examined for its possible effects on cell proliferation in both normal and malignant cells. METHODS: In vitro (cell cultures) and in vivo (xenotransplants) experiments were performed. RESULTS: Phenanthridine-derived PARP inhibitors interfered with cell proliferation by causing G2/M arrest in both normal (human epithelial cells MCF10A and mouse embryonic fibroblasts) and human breast cancer cells MCF-7 and MDA231. However, whereas the normal cells were only transiently arrested, G2/M arrest in the malignant breast cancer cells was permanent and was accompanied by a massive cell death. In accordance, treatment with a phenanthridine-derived PARP inhibitor prevented the development of MCF-7 and MDA231 xenotransplants in female nude mice. Quiescent cells (neurons and cardiomyocytes) are not impaired by these PARP inhibitors. CONCLUSIONS: These results outline a new therapeutic approach for a selective eradication of abundant nonhereditary human breast cancers

Testing Human Sperm Chemotaxis: How to Detect Biased Motion in Population Assays

Biased motion of motile cells in a concentration gradient of a chemoattractant is frequently studied on the population level. This approach has been particularly employed in human sperm chemotactic assays, where the fraction of responsive cells is low and detection of biased motion depends on subtle differences. In these assays, statistical measures such as population odds ratios of swimming directions can be employed to infer chemotactic performance. Here, we report on an improved method to assess statistical significance of experimentally determined odds ratios and discuss the strong impact of data correlations that arise from the directional persistence of sperm swimming

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Why honey is effective as a medicine. 1. Its use in modern medicine

Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered