Potable to poisonous: An analysis of the Flint, Michigan water crisis

Flint, Michigan, switched its drinking water source from Lake Huron to the Flint River in April 2014 to cut costs after a projected deficit. When an accumulation of lead and bacteria contamination was discovered over a year after the switch, Michigan was declared to be in a Federal State of Emergency. This case study investigates the events and actions leading to both the water contamination and public exposure of the crisis, as well as explores how the constituents responded and continue to be impacted by the events

Robustness of Image-Based Malware Classification Models Trained with Generative Adversarial Networks

As malware continues to evolve, deep learning models are increasingly used for malware detection and classification, including image based classification. However, adversarial attacks can be used to perturb images so as to evade detection by these models. This study investigates the effectiveness of training deep learning models with Generative Adversarial Network-generated data to improve their robustness against such attacks. Two image conversion methods, byte plot and space-filling curves, were used to represent the malware samples, and a ResNet-50 architecture was used to train models on the image datasets. The models were then tested against a projected gradient descent attack. It was found that without GAN generated data, the models’ prediction performance drastically decreased from 93-95% to 4.5% accuracy. However, the addition of adversarial images to the training data almost doubled the accuracy of the models. This study highlights the potential benefits of incorporating GAN-generated data in the training of deep learning models to improve their robustness against adversarial attacks

Hackers and the Dark Net: A Look into Hacking and the Deep Web

The dark web is notorious for the illicit activities it facilitates, including human trafficking, narcotics and weapons sales, and illegally obtained information transfers. In order to combat this constant, invisible threat to security, governments and experts have called for tougher legislation and increased surveillance. But on the opposite end of all this crime and villainy lie persecuted groups who use the dark web and the anonymity it affords to protect themselves from retaliation. This article uses Atavist’s digital storytelling medium to explore how hackers “hack” the web, ethical questions surrounding the dark web, and policy solutions to cyber security

Autophagy prevents early proinflammatory responses and neutrophil recruitment during Mycobacterium tuberculosis infection without affecting pathogen burden in macrophages

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment during M. tuberculosis infection, we used different mouse strains that conditionally delete Atg5 in specific cell types. We found that ATG5 is required in CD11c+ cells (lung macrophages and dendritic cells) to control the production of proinflammatory cytokines and chemokines during M. tuberculosis infection, which would otherwise promote neutrophil recruitment. This role for ATG5 is autophagy dependent, but independent of mitophagy, LC3-associated phagocytosis, and inflammasome activation, which are the most well-characterized ways that autophagy proteins regulate inflammation. In addition to the increased proinflammatory cytokine production from macrophages during M. tuberculosis infection, loss of ATG5 in innate immune cells also results in an early induction of TH17 responses. Despite prior published in vitro cell culture experiments supporting a role for autophagy in controlling M. tuberculosis replication in macrophages, the effects of autophagy on inflammatory responses occur without changes in M. tuberculosis burden in macrophages. These findings reveal new roles for autophagy proteins in lung resident macrophages and dendritic cells that are required to suppress inflammatory responses that are associated with poor control of M. tuberculosis infection

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy

Funder: The Republic of Cyprus through the Research and Innovation Foundation Foundation (Project: CULTURE/BR-NE/0416/07)Funder: Wallenberg Scholar and the fluid biomarker measurements in the lab of HZ and AJH were supported by the UK Dementia Research Institute at UCLAbstract: Mutations in the GJB1 gene, encoding the gap junction (GJ) protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We developed a gene therapy approach for CMT1X using an AAV9 vector to deliver the GJB1/Cx32 gene under the myelin protein zero (Mpz) promoter for targeted expression in Schwann cells. Lumbar intrathecal injection of the AAV9-Mpz.GJB1 resulted in widespread biodistribution in the peripheral nervous system including lumbar roots, sciatic and femoral nerves, as well as in Cx32 expression in the paranodal non-compact myelin areas of myelinated fibers. A pre-, as well as post-onset treatment trial in Gjb1-null mice, demonstrated improved motor performance and sciatic nerve conduction velocities along with improved myelination and reduced inflammation in peripheral nerve tissues. Blood biomarker levels were also significantly ameliorated in treated mice. This study provides evidence that a clinically translatable AAV9-mediated gene therapy approach targeting Schwann cells could potentially treat CMT1X

The Fluctuating Phenotype of the Lymphohematopoietic Stem Cell with Cell Cycle Transit

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2–4-h intervals of culture over 24–48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2–4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting

Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS study

<p>Abstract</p> <p>Background</p> <p>Obesity among children and adolescents is a growing public health problem. The aim of the present paper is to identify potential determinants of obesity and risk groups among 3- to 17-year old children and adolescents to provide a basis for effective prevention strategies.</p> <p>Methods</p> <p>Data were collected in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), a nationally representative and comprehensive data set on health behaviour and health status of German children and adolescents. Body height and weight were measured and body mass index (BMI) was classified according to IOTF cut-off points. Statistical analyses were conducted on 13,450 non-underweight children and adolescents aged 3 to 17 years. The association between overweight, obesity and several potential determinants was analysed for this group as well as for three socio-economic status (SES) groups. A multiple logistic regression model with obesity as the dependent variable was also calculated.</p> <p>Results</p> <p>The strongest association with obesity was observed for parental overweight and for low SES. Furthermore, a positive association with both overweight (including obesity) and obesity was seen for maternal smoking during pregnancy, high weight gain during pregnancy (only for mothers of normal weight), high birth weight, and high media consumption. In addition, high intakes of meat and sausages, total beverages, water and tea, total food and beverages, as well as energy-providing food and beverages were significantly associated with overweight as well as with obesity. Long sleep time was negatively associated with obesity among 3- to 10-year olds. Determinants of obesity occurred more often among children and adolescents with low SES.</p> <p>Conclusion</p> <p>Parental overweight and a low SES are major potential determinants of obesity. Families with these characteristics should be focused on in obesity prevention.</p

Pain control after total knee arthroplasty: a randomized trial comparing local infiltration anesthesia and continuous femoral block

Local infiltration analgesia (LIA) is a new multimodal wound infiltration method. It has attracted growing interest in recent years and is widely used all over the world for treating postoperative pain after knee and hip arthroplasty. This method is based on systematic infiltration of a mixture of ropivacaine, a long acting local anesthetic, ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures subject to surgical trauma inknee and hip arthroplasty. Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty (TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to the work presented in this thesis. In a randomized trial the efficacy of LIA in TKA with regard to pain at rest and upon movement was compared to femoral block. Both methods result in a high quality pain relief and similar morphine consumption, but fewer patients in the LIA group reported pain of 7/10 on any occasion during the 24 h monitoring period (paper I). In the same patient cohort the maximal total plasma concentration of ropivacaine was below the established toxic threshold for most patients although a few reached potentially toxic concentrations of 1.4-1.7 mg/L. The time to maximal detected plasma concentration was around 4-6 h after release of tourniquet in TKA (paper II). All patients in the THA cohort were subjected to the routine LIA protocol. In these patients both the total and unbound plasma concentration of ropivacaine was determined. The concentration was below the established toxic threshold. As ropivacaine binds to a-1 acid glycoprotein(AAG) we assessed the possibility that increased AAG may decrease the unbound concentration of ropivacaine. A40 % increase in AAG was detected during the first 24 h after surgery, however the fraction of unbound ropivacaine remained the same. There was a trend towards increased C max of ropivacaine with increasing age and decreasing creatinine clearance but the statistical power was too low to draw any conclusion (paper III). Administration of 30mg ketorolac according to the LIA protocol both in TKA and THA resulted in a similar Cmax as previously reported after 10 mg intramuscular ketorolac (paper II, paper IV). Neither age, nor body weight or BMI, nor creatinine clearance, correlates to maximal ketorolac plasma concentration or total exposure to ketorolac (AUC) (paper IV). In conclusion, LIA provides good postoperative analgesia which is similar to femoral block after total knee arthroplasty. The plasma concentration of ropivacaine seems to be below toxic levels in most TKA patients. The unbound plasma concentration of ropivcaine in THA seems to be below the toxic level. The use of ketorolac in LIA may not be safer than other routes of administration, and similar restrictions should be applied in patients at risk of developing side effects

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses